rs6581511

chr12-63884322-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+39439G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.924 in 152,192 control chromosomes in the GnomAD database, including 65,078 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 0.92 (65078 hom., cov: 31)
• Consequence: SRGAP1 NM_020762.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRGAP1	NM_020762.4	c.67+39439G>T		intron_variant		ENST00000355086.8
SRGAP1	NM_001346201.2	c.67+39439G>T		intron_variant
SRGAP1	XM_024449096.2	c.67+39439G>T		intron_variant
SRGAP1	XM_024449097.2	c.67+39439G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRGAP1	ENST00000355086.8	c.67+39439G>T		intron_variant		1	NM_020762.4	A1
SRGAP1	ENST00000631006.3	c.67+39439G>T		intron_variant		5		P3
SRGAP1	ENST00000695902.1	c.67+39439G>T		intron_variant, NMD_transcript_variant
SRGAP1	ENST00000537556.1	n.81+39439G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.924 AC: 140453 AN: 152074 Hom.: 65020 Cov.: 31

Gnomad AFR AF: 0.977

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.903

Gnomad ASJ AF: 0.965

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.891

Gnomad FIN AF: 0.937

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.896

Gnomad OTH AF: 0.937

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

GnomAD4 genome AF: 0.924 AC: 140570 AN: 152192 Hom.: 65078 Cov.: 31 AF XY: 0.926 AC XY: 68865 AN XY: 74388

Gnomad4 AFR AF: 0.977

Gnomad4 AMR AF: 0.903

Gnomad4 ASJ AF: 0.965

Gnomad4 EAS AF: 0.917

Gnomad4 SAS AF: 0.892

Gnomad4 FIN AF: 0.937

Gnomad4 NFE AF: 0.896

Gnomad4 OTH AF: 0.936

Alfa AF: 0.909 Hom.: 64961

Bravo AF: 0.922

Asia WGS AF: 0.877 AC: 3048 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	4.1
Dann	Benign	0.43

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: rs6581511; hg19: chr12-64278102;