rs6683027

Positions:

• chr1-206423548-G-A
• chr1-206423548-G-C
• chr1-206423548-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.1494+2274G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,846 control chromosomes in the GnomAD database, including 16,759 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 0.47 (16759 hom., cov: 31)
• Consequence: SRGAP2 NM_015326.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRGAP2	NM_015326.5	c.1494+2274G>A		intron_variant		ENST00000573034.8	NP_056141.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRGAP2	ENST00000573034.8	c.1494+2274G>A		intron_variant		1	NM_015326.5	ENSP00000459615.2
SRGAP2	ENST00000624873.3	c.1491+2274G>A		intron_variant		1		ENSP00000485517.1
SRGAP2	ENST00000605476.5	c.336+2274G>A		intron_variant		1		ENSP00000474270.1
SRGAP2	ENST00000605610.5	c.1491+2274G>A		intron_variant		2		ENSP00000473954.1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70597 AN: 151728 Hom.: 16755 Cov.: 31

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.465 AC: 70633 AN: 151846 Hom.: 16759 Cov.: 31 AF XY: 0.471 AC XY: 34958 AN XY: 74184

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.437

Alfa AF: 0.300 Hom.: 707

Bravo AF: 0.465

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0060
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6683027; hg19: chr1-206596899; COSMIC: COSV55335028;