rs72793372

Variant summary

Our verdict is Benign. Variant got -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:7

Conservation

PhyloP100: -0.220

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chr16-30707552-C-T is described in Lovd as [Benign].

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/exons	MANE	UniProt
SRCAP	NM_006662.3 linkuse as main transcript	c.493-20C>T		intron_variant		ENST00000262518.9

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
SRCAP	ENST00000262518.9 linkuse as main transcript	c.493-20C>T	intron_variant	2	NM_006662.3	P1	Q6ZRS2-1
SRCAP	ENST00000411466.7 linkuse as main transcript	c.493-20C>T	intron_variant	3		P1	Q6ZRS2-1
SRCAP	ENST00000706321.1 linkuse as main transcript	c.493-20C>T	intron_variant			P1	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

GnomAD3 exomes

AF:

0.149

AC:

36377

AN:

243938

Hom.:

3350

AF XY:

0.151

AC XY:

19892

AN XY:

131782

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 SAS exome

AF:

0.0882

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

Gnomad4 AFR exome

AF:

0.0370

Gnomad4 AMR exome

AF:

0.113

Gnomad4 ASJ exome

AF:

0.132

Gnomad4 EAS exome

AF:

0.000781

Gnomad4 SAS exome

AF:

0.0905

Gnomad4 FIN exome

AF:

0.203

Gnomad4 NFE exome

AF:

0.222

Gnomad4 OTH exome

AF:

0.181

GnomAD4 genome

AF:

0.149

AC:

22707

AN:

152118

Hom.:

2205

Cov.:

AF XY:

0.147

AC XY:

10965

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0453

Gnomad4 AMR

AF:

0.150

Gnomad4 ASJ

AF:

0.146

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0799

Gnomad4 FIN

AF:

0.222

Gnomad4 NFE

AF:

0.217

Gnomad4 OTH

AF:

0.145

Alfa

AF:

0.185

Hom.:

716

Bravo

AF:

0.138

Asia WGS

AF:

0.0460

AC:

160

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 07, 2020	- -

Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Floating-Harbor syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

Cadd

Benign

1.7

Dann

Benign

0.63

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over