NM_015326.5:c.1556-197G>A

Variant names:

• chr1-206436768-G-A
• rs10494876
• NM_015326.5:c.1556-197G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SRGAP2	NM_015326.5	c.1556-197G>A		intron_variant	Intron 14 of 22	ENST00000573034.8	NP_056141.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRGAP2	ENST00000573034.8	c.1556-197G>A		intron_variant	Intron 14 of 22	1	NM_015326.5	ENSP00000459615.2
SRGAP2	ENST00000624873.3	c.1553-197G>A		intron_variant	Intron 13 of 21	1		ENSP00000485517.1
SRGAP2	ENST00000605476.5	c.398-197G>A		intron_variant	Intron 5 of 11	1		ENSP00000474270.1
SRGAP2	ENST00000605610.5	c.1553-197G>A		intron_variant	Intron 13 of 19	2		ENSP00000473954.1

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

African (AFR) AF: 0.250 AC: 10355 AN: 41502

American (AMR) AF: 0.0509 AC: 779 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0317 AC: 110 AN: 3472

East Asian (EAS) AF: 0.0121 AC: 63 AN: 5186

South Asian (SAS) AF: 0.0342 AC: 165 AN: 4830

European-Finnish (FIN) AF: 0.0410 AC: 435 AN: 10610

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0285 AC: 1935 AN: 68012

Other (OTH) AF: 0.0851 AC: 180 AN: 2116

Alfa AF: 0.0392 Hom.: 358

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
PhyloP100		-0.16

Splicing

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

Other links and lift over

dbSNP: rs10494876; hg19: chr1-206610118;