rs7187691

Variant names:

• chr16-30700467-G-C
• rs7187691
• NM_006662.3:c.-209-149G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-30700467-G-C
• chr16-30700467-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006662.3(SRCAP):​c.-209-149G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 193,842 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (61 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (3 hom.)
• Consequence: SRCAP NM_006662.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.126
• Publications: 0 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
• Floating-Harbor syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Ambry Genetics, PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-30700467-G-C is Benign according to our data. Variant chr16-30700467-G-C is described in ClinVar as Benign. ClinVar VariationId is 1268985.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0149 (2265/152280) while in subpopulation AFR AF = 0.0509 (2114/41536). AF 95% confidence interval is 0.0491. There are 61 homozygotes in GnomAd4. There are 1073 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2265 AD gene.

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.-209-149G>C		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.-209-149G>C		intron	N/A	ENSP00000262518.4	Q6ZRS2-1
	SRCAP	ENST00000411466.7	TSL:3	c.-209-149G>C		intron	N/A	ENSP00000405186.3	C9J4U4
	SRCAP	ENST00000706321.1		c.-209-149G>C		intron	N/A	ENSP00000516346.1	Q6ZRS2-1

Frequencies

GnomAD3 genomes AF: 0.0149 AC: 2261 AN: 152162 Hom.: 61 Cov.: 33

Gnomad AFR AF: 0.0509

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00668

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0119

GnomAD4 exome AF: 0.00233 AC: 97 AN: 41562 Hom.: 3 AF XY: 0.00210 AC XY: 45 AN XY: 21472

African (AFR) AF: 0.0507 AC: 75 AN: 1480

American (AMR) AF: 0.00337 AC: 10 AN: 2970

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1342

East Asian (EAS) AF: 0.00 AC: 0 AN: 2836

South Asian (SAS) AF: 0.00 AC: 0 AN: 4494

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1206

Middle Eastern (MID) AF: 0.00610 AC: 1 AN: 164

European-Non Finnish (NFE) AF: 0.0000813 AC: 2 AN: 24596

Other (OTH) AF: 0.00364 AC: 9 AN: 2474

GnomAD4 genome AF: 0.0149 AC: 2265 AN: 152280 Hom.: 61 Cov.: 33 AF XY: 0.0144 AC XY: 1073 AN XY: 74468

African (AFR) AF: 0.0509 AC: 2114 AN: 41536

American (AMR) AF: 0.00667 AC: 102 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68022

Other (OTH) AF: 0.0118 AC: 25 AN: 2116

Alfa AF: 0.00296 Hom.: 1

Bravo AF: 0.0168

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.14
DANN	Benign	0.62
PhyloP100		-0.13
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: rs7187691; hg19: chr16-30711788;