16-30701000-C-A

Position:

• chr16-30701000-C-A

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.54+122C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00739 in 943,688 control chromosomes in the GnomAD database, including 312 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (189 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (123 hom.)
• Consequence: SRCAP NM_006662.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.300

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=-0.88).
• BP6: Variant 16-30701000-C-A is Benign according to our data. Variant chr16-30701000-C-A is described in ClinVar as [Benign]. Clinvar id is 1304889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRCAP	NM_006662.3	c.54+122C>A		intron_variant		ENST00000262518.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRCAP	ENST00000262518.9	c.54+122C>A		intron_variant		2	NM_006662.3	P1
SRCAP	ENST00000411466.7	c.54+122C>A		intron_variant		3		P1
SRCAP	ENST00000706321.1	c.54+122C>A		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.0290 AC: 4405 AN: 152096 Hom.: 183 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00550

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.0182

GnomAD4 exome AF: 0.00320 AC: 2535 AN: 791474 Hom.: 123 AF XY: 0.00266 AC XY: 1085 AN XY: 407842

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.00462

Gnomad4 ASJ exome AF: 0.00142

Gnomad4 EAS exome AF: 0.00131

Gnomad4 SAS exome AF: 0.000176

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000108

Gnomad4 OTH exome AF: 0.00558

GnomAD4 genome AF: 0.0291 AC: 4435 AN: 152214 Hom.: 189 Cov.: 32 AF XY: 0.0282 AC XY: 2100 AN XY: 74428

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.00543

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.0241 Hom.: 17

Bravo AF: 0.0329

Asia WGS AF: 0.00953 AC: 34 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 23, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.77
DANN	Benign	0.50

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: rs73536499; hg19: chr16-30712321;