rs72793372

Positions:

• chr16-30707552-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.220

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]

ACMG classification

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	Protein	UniProt
SRCAP	NM_006662.3	c.493-20C>T		intron_variant		ENST00000262518.9	NP_006653.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRCAP	ENST00000262518.9	c.493-20C>T		intron_variant		2	NM_006662.3	ENSP00000262518	P1
SRCAP	ENST00000411466.7	c.493-20C>T		intron_variant		3		ENSP00000405186	P1
SRCAP	ENST00000706321.1	c.493-20C>T		intron_variant				ENSP00000516346	P1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22708 AN: 152000 Hom.: 2205 Cov.: 32

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

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.: 33 AF XY: 0.194 AC XY: 140975 AN XY: 725018

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.: 32 AF XY: 0.147 AC XY: 10965 AN XY: 74384

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:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

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

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	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

Other links and lift over

dbSNP: rs72793372; hg19: chr16-30718873; COSMIC: COSV52673831; COSMIC: COSV52673831;