rs72793372

Variant names:

• chr16-30707552-C-T
• rs72793372
• NM_006662.3:c.493-20C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000282034 (HGNC:):

ACMG classification

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006662.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRCAP	NM_006662.3	MANE Select	c.493-20C>T		intron	N/A	NP_006653.2	Q6ZRS2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRCAP	ENST00000262518.9	TSL:2 MANE Select	c.493-20C>T		intron	N/A	ENSP00000262518.4	Q6ZRS2-1
	ENSG00000282034	ENST00000380361.7	TSL:2	n.436-20C>T		intron	N/A	ENSP00000369719.3	A0A0C4DFX4
	SRCAP	ENST00000411466.7	TSL:3	c.493-20C>T		intron	N/A	ENSP00000405186.3	C9J4U4

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

GnomAD2 exomes AF: 0.149 AC: 36377 AN: 243938 AF XY: 0.151

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

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: 31 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

GnomAD4 genome AF: 0.149 AC: 22707 AN: 152118 Hom.: 2205 Cov.: 32 AF XY: 0.147 AC XY: 10965 AN XY: 74384

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: 6 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: 39 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14776 AN: 67978

Other (OTH) AF: 0.145 AC: 306 AN: 2110

Alfa AF: 0.181 Hom.: 1536

Bravo AF: 0.138

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	1	Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities (1)
-	-	1	Floating-Harbor syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.63
PhyloP100		-0.22
PromoterAI		-0.015	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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