rs75991082

chr16-30733886-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_006662.3(SRCAP):c.6495-8C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00171 in 1,613,810 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0091 (25 hom., cov: 32)
  • Exomes 𝑓: 0.00095 (22 hom.)
• Consequence: SRCAP NM_006662.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0003717
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.167

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=-0.83).
• BP6: Variant 16-30733886-C-A is Benign according to our data. Variant chr16-30733886-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 318890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-30733886-C-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00908 (1382/152244) while in subpopulation AFR AF= 0.0309 (1282/41538). AF 95% confidence interval is 0.0295. There are 25 homozygotes in gnomad4. There are 651 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1380 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRCAP	NM_006662.3	c.6495-8C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000262518.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRCAP	ENST00000262518.9	c.6495-8C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2	NM_006662.3	P1
SRCAP	ENST00000411466.7	c.6495-8C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		3		P1
SRCAP	ENST00000706321.1	c.6495-8C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.00907 AC: 1380 AN: 152126 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.0309

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00814

GnomAD3 exomes AF: 0.00237 AC: 594 AN: 251060 Hom.: 11 AF XY: 0.00168 AC XY: 228 AN XY: 135694

Gnomad AFR exome AF: 0.0316

Gnomad AMR exome AF: 0.00145

Gnomad ASJ exome AF: 0.0000995

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.000946 AC: 1382 AN: 1461566 Hom.: 22 Cov.: 32 AF XY: 0.000805 AC XY: 585 AN XY: 727096

Gnomad4 AFR exome AF: 0.0333

Gnomad4 AMR exome AF: 0.00179

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000396

Gnomad4 OTH exome AF: 0.00207

GnomAD4 genome AF: 0.00908 AC: 1382 AN: 152244 Hom.: 25 Cov.: 32 AF XY: 0.00875 AC XY: 651 AN XY: 74436

Gnomad4 AFR AF: 0.0309

Gnomad4 AMR AF: 0.00458

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00806

Alfa AF: 0.00465 Hom.: 4

Bravo AF: 0.0104

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 03, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 22, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.99
Dann	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00037
dbscSNV1_RF	Benign	0.14
SpliceAI score (max)		0.040		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: rs75991082; hg19: chr16-30745207;