rs10494876

Positions:

• chr1-206436768-G-A
• chr1-206436768-G-T

Variant summary

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

The NM_015326.5(SRGAP2):​c.1556-197G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0922 in 152,232 control chromosomes in the GnomAD database, including 1,377 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 0.092 (1377 hom., cov: 32)
• Consequence: SRGAP2 NM_015326.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.157

Genes affected

SRGAP2 (HGNC:19751): (SLIT-ROBO Rho GTPase activating protein 2) This locus encodes a member of the SLIT-ROBO Rho GTPase activating protein family. The encoded protein stimulates GTPase activity of Rac1, and plays a role in cortical neuron development. This locus has several paralogs on human chromosome 1 resulting from segmental duplication. While this locus itself is conserved among various species, the paralogs are found only in the genus Homo, and not in the genomes of non-human great apes. Alternatively spliced transcript variants have been described for this locus. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRGAP2	NM_015326.5	c.1556-197G>A		intron_variant		ENST00000573034.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRGAP2	ENST00000573034.8	c.1556-197G>A		intron_variant		1	NM_015326.5	P5
SRGAP2	ENST00000605476.5	c.398-197G>A		intron_variant		1
SRGAP2	ENST00000624873.3	c.1553-197G>A		intron_variant		1		A1
SRGAP2	ENST00000605610.5	c.1553-197G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0921 AC: 14003 AN: 152114 Hom.: 1370 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0510

Gnomad ASJ AF: 0.0317

Gnomad EAS AF: 0.0121

Gnomad SAS AF: 0.0341

Gnomad FIN AF: 0.0410

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0284

Gnomad OTH AF: 0.0860

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

GnomAD4 genome AF: 0.0922 AC: 14042 AN: 152232 Hom.: 1377 Cov.: 32 AF XY: 0.0908 AC XY: 6760 AN XY: 74448

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.0509

Gnomad4 ASJ AF: 0.0317

Gnomad4 EAS AF: 0.0121

Gnomad4 SAS AF: 0.0342

Gnomad4 FIN AF: 0.0410

Gnomad4 NFE AF: 0.0285

Gnomad4 OTH AF: 0.0851

Alfa AF: 0.0313 Hom.: 35

Bravo AF: 0.101

Asia WGS AF: 0.0400 AC: 142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.45

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10494876; hg19: chr1-206610118;