rs7971621

chr12-63866834-G-Achr12-63866834-G-Cchr12-63866834-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020762.4(SRGAP1):c.67+21951G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.971 in 151,588 control chromosomes in the GnomAD database, including 71,528 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.97 (71528 hom., cov: 27)
• Consequence: SRGAP1 NM_020762.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.699

Genes affected

SRGAP1 (HGNC:17382): (SLIT-ROBO Rho GTPase activating protein 1) The protein encoded by this gene is a GTPase activator, working with the GTPase CDC42 to negatively regulate neuronal migration. The encoded protein interacts with the transmembrane receptor ROBO1 to inactivate CDC42. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.983 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRGAP1	NM_020762.4	c.67+21951G>A		intron_variant		ENST00000355086.8
SRGAP1	NM_001346201.2	c.67+21951G>A		intron_variant
SRGAP1	XM_024449096.2	c.67+21951G>A		intron_variant
SRGAP1	XM_024449097.2	c.67+21951G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRGAP1	ENST00000355086.8	c.67+21951G>A		intron_variant		1	NM_020762.4	A1
SRGAP1	ENST00000631006.3	c.67+21951G>A		intron_variant		5		P3
SRGAP1	ENST00000695902.1	c.67+21951G>A		intron_variant, NMD_transcript_variant
SRGAP1	ENST00000537556.1	n.81+21951G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.971 AC: 147110 AN: 151476 Hom.: 71473 Cov.: 27

Gnomad AFR AF: 0.991

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.987

Gnomad ASJ AF: 0.986

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.971

Gnomad FIN AF: 0.981

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.951

Gnomad OTH AF: 0.978

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.971 AC: 147221 AN: 151588 Hom.: 71528 Cov.: 27 AF XY: 0.973 AC XY: 72071 AN XY: 74044

Gnomad4 AFR AF: 0.991

Gnomad4 AMR AF: 0.987

Gnomad4 ASJ AF: 0.986

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.971

Gnomad4 FIN AF: 0.981

Gnomad4 NFE AF: 0.951

Gnomad4 OTH AF: 0.978

Alfa AF: 0.959 Hom.: 14197

Bravo AF: 0.973

Asia WGS AF: 0.986 AC: 3429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.75
Dann	Benign	0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7971621; hg19: chr12-64260614;