16-30737303-C-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_006662.3(SRCAP):​c.7263C>A​(p.Arg2421Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,614,060 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 35 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 32 hom. )

Consequence

SRCAP
NM_006662.3 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0340
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 16-30737303-C-A is Benign according to our data. Variant chr16-30737303-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 160037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.034 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0129 (1960/152168) while in subpopulation AFR AF = 0.0428 (1777/41510). AF 95% confidence interval is 0.0412. There are 35 homozygotes in GnomAd4. There are 919 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High AC in GnomAd4 at 1960 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SRCAPNM_006662.3 linkc.7263C>A p.Arg2421Arg synonymous_variant Exon 34 of 34 ENST00000262518.9 NP_006653.2 Q6ZRS2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SRCAPENST00000262518.9 linkc.7263C>A p.Arg2421Arg synonymous_variant Exon 34 of 34 2 NM_006662.3 ENSP00000262518.4 Q6ZRS2-1
ENSG00000282034ENST00000380361.7 linkn.6732C>A non_coding_transcript_exon_variant Exon 29 of 31 2 ENSP00000369719.3 A0A0C4DFX4

Frequencies

GnomAD3 genomes
AF:
0.0129
AC:
1954
AN:
152050
Hom.:
34
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0427
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00936
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.0115
GnomAD2 exomes
AF:
0.00333
AC:
835
AN:
250870
AF XY:
0.00231
show subpopulations
Gnomad AFR exome
AF:
0.0434
Gnomad AMR exome
AF:
0.00289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000141
Gnomad OTH exome
AF:
0.00228
GnomAD4 exome
AF:
0.00127
AC:
1860
AN:
1461892
Hom.:
32
Cov.:
31
AF XY:
0.00109
AC XY:
794
AN XY:
727248
show subpopulations
African (AFR)
AF:
0.0430
AC:
1438
AN:
33480
American (AMR)
AF:
0.00342
AC:
153
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.0000232
AC:
2
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
0.00433
AC:
25
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000585
AC:
65
AN:
1112012
Other (OTH)
AF:
0.00293
AC:
177
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.477
Heterozygous variant carriers
0
147
293
440
586
733
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
50
100
150
200
250
<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:
0.0129
AC:
1960
AN:
152168
Hom.:
35
Cov.:
32
AF XY:
0.0124
AC XY:
919
AN XY:
74388
show subpopulations
African (AFR)
AF:
0.0428
AC:
1777
AN:
41510
American (AMR)
AF:
0.00929
AC:
142
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5154
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4810
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10618
Middle Eastern (MID)
AF:
0.0102
AC:
3
AN:
294
European-Non Finnish (NFE)
AF:
0.000206
AC:
14
AN:
68000
Other (OTH)
AF:
0.0114
AC:
24
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
98
196
293
391
489
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
20
40
60
80
100
<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:
0.00456
Hom.:
9
Bravo
AF:
0.0146
Asia WGS
AF:
0.00520
AC:
18
AN:
3478
EpiCase
AF:
0.000273
EpiControl
AF:
0.000178

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
May 05, 2021
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

See Variant Classification Assertion Criteria. -

Jan 30, 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

- -

not specified Benign:1
Feb 08, 2013
Genetic Services Laboratory, University of Chicago
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
-0.49
CADD
Benign
2.9
DANN
Benign
0.73
PhyloP100
0.034
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs74947321; hg19: chr16-30748624; API