chr16-30707552-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006662.3(SRCAP):c.493-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,610,278 control chromosomes in the GnomAD database, including 33,338 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2205 hom., cov: 32)

Exomes 𝑓: 0.20 ( 31133 hom. )

Consequence

SRCAP
NM_006662.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.220

Publications

6 publications found

Variant links:

Genes affected

SRCAP (HGNC:16974): (Snf2 related CREBBP activator protein) This gene encodes the core catalytic component of the multiprotein chromatin-remodeling SRCAP complex. The encoded protein is an ATPase that is necessary for the incorporation of the histone variant H2A.Z into nucleosomes. It can function as a transcriptional activator in Notch-mediated, CREB-mediated and steroid receptor-mediated transcription. Mutations in this gene cause Floating-Harbor syndrome, a rare disorder characterized by short stature, language deficits and dysmorphic facial features. [provided by RefSeq, Feb 2012]

SRCAP Gene-Disease associations (from GenCC):

developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
Floating-Harbor syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

SRCAP links:

ENSG00000282034 (HGNC:):

ENSG00000282034 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 16-30707552-C-T is Benign according to our data. Variant chr16-30707552-C-T is described in ClinVar as [Benign]. Clinvar id is 260018.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRCAP	NM_006662.3 link	c.493-20C>T		intron_variant	Intron 5 of 33	ENST00000262518.9	NP_006653.2	Q6ZRS2-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SRCAP	ENST00000262518.9 link	c.493-20C>T	intron_variant	Intron 5 of 33	2	NM_006662.3	ENSP00000262518.4	Q6ZRS2-1
ENSG00000282034	ENST00000380361.7 link	n.436-20C>T	intron_variant	Intron 2 of 30	2		ENSP00000369719.3	A0A0C4DFX4
SRCAP	ENST00000411466.7 link	c.493-20C>T	intron_variant	Intron 5 of 33	3		ENSP00000405186.3	Q6ZRS2-1C9J4U4
SRCAP	ENST00000706321.1 link	c.493-20C>T	intron_variant	Intron 5 of 33			ENSP00000516346.1	Q6ZRS2-1

Frequencies

GnomAD3 genomes

AF:

0.149

AC:

22708

AN:

152000

Hom.:

2205

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0453

Gnomad AMI

AF:

0.181

Gnomad AMR

AF:

0.151

Gnomad ASJ

AF:

0.146

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0790

Gnomad FIN

AF:

0.222

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.146

GnomAD2 exomes

AF:

0.149

AC:

36377

AN:

243938

AF XY:

0.151

show subpopulations

Gnomad AFR exome

AF:

0.0386

Gnomad AMR exome

AF:

0.110

Gnomad ASJ exome

AF:

0.137

Gnomad EAS exome

AF:

0.000610

Gnomad FIN exome

AF:

0.212

Gnomad NFE exome

AF:

0.206

Gnomad OTH exome

AF:

0.162

GnomAD4 exome

AF:

0.197

AC:

286825

AN:

1458160

Hom.:

31133

Cov.:

AF XY:

0.194

AC XY:

140975

AN XY:

725018

show subpopulations

African (AFR)

AF:

0.0370

AC:

1236

AN:

33444

American (AMR)

AF:

0.113

AC:

4957

AN:

43936

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

3428

AN:

26046

East Asian (EAS)

AF:

0.000781

AC:

AN:

39668

South Asian (SAS)

AF:

0.0905

AC:

7779

AN:

85914

European-Finnish (FIN)

AF:

0.203

AC:

10818

AN:

53228

Middle Eastern (MID)

AF:

0.128

AC:

716

AN:

5586

European-Non Finnish (NFE)

AF:

0.222

AC:

246979

AN:

1110120

Other (OTH)

AF:

0.181

AC:

10881

AN:

60218

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

12261

24522

36783

49044

61305

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8228

16456

24684

32912

41140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.149

AC:

22707

AN:

152118

Hom.:

2205

Cov.:

AF XY:

0.147

AC XY:

10965

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.0453

AC:

1880

AN:

41492

American (AMR)

AF:

0.150

AC:

2298

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.146

AC:

507

AN:

3470

East Asian (EAS)

AF:

0.00116

AC:

AN:

5186

South Asian (SAS)

AF:

0.0799

AC:

385

AN:

4820

European-Finnish (FIN)

AF:

0.222

AC:

2345

AN:

10578

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.217

AC:

14776

AN:

67978

Other (OTH)

AF:

0.145

AC:

306

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

946

1891

2837

3782

4728

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

258

516

774

1032

1290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.181

Hom.:

1536

Bravo

AF:

0.138

Asia WGS

AF:

0.0460

AC:

160

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

May 07, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Floating-Harbor syndrome

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.7

(source)

DANN

Benign

0.63

PhyloP100

-0.22

PromoterAI

-0.015

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over