rs6701879

Positions:

• chr1-206444420-T-C

Variant summary

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

The ENST00000573034.8(SRGAP2):​c.1875-1655T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,126 control chromosomes in the GnomAD database, including 3,124 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 0.20 (3124 hom., cov: 32)
• Consequence: SRGAP2 ENST00000573034.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.715

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRGAP2	NM_015326.5	c.1875-1655T>C		intron_variant		ENST00000573034.8	NP_056141.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRGAP2	ENST00000573034.8	c.1875-1655T>C		intron_variant		1	NM_015326.5	ENSP00000459615	P5

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29663 AN: 152008 Hom.: 3114 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.0681

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.195 AC: 29684 AN: 152126 Hom.: 3124 Cov.: 32 AF XY: 0.198 AC XY: 14716 AN XY: 74362

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.0689

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.169

Alfa AF: 0.189 Hom.: 461

Bravo AF: 0.186

Asia WGS AF: 0.213 AC: 739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.90
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6701879; hg19: chr1-206617766;