rs11175194

Positions:

• chr12-63871057-G-A
• chr12-63871057-G-C

Variant summary

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

The ENST00000355086.8(SRGAP1):​c.67+26174G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,058 control chromosomes in the GnomAD database, including 2,831 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 0.16 (2831 hom., cov: 32)
• Consequence: SRGAP1 ENST00000355086.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.563

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRGAP1	NM_020762.4	c.67+26174G>A		intron_variant		ENST00000355086.8	NP_065813.1
SRGAP1	NM_001346201.2	c.67+26174G>A		intron_variant			NP_001333130.1
SRGAP1	XM_024449096.2	c.67+26174G>A		intron_variant			XP_024304864.1
SRGAP1	XM_024449097.2	c.67+26174G>A		intron_variant			XP_024304865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRGAP1	ENST00000355086.8	c.67+26174G>A		intron_variant		1	NM_020762.4	ENSP00000347198	A1
SRGAP1	ENST00000631006.3	c.67+26174G>A		intron_variant		5		ENSP00000485752	P3
SRGAP1	ENST00000695902.1	c.67+26174G>A		intron_variant, NMD_transcript_variant				ENSP00000512252
SRGAP1	ENST00000537556.1	n.81+26174G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23565 AN: 151940 Hom.: 2817 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0534

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0584

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.155 AC: 23616 AN: 152058 Hom.: 2831 Cov.: 32 AF XY: 0.163 AC XY: 12136 AN XY: 74334

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.0534

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.0584

Gnomad4 OTH AF: 0.125

Alfa AF: 0.0736 Hom.: 1442

Bravo AF: 0.157

Asia WGS AF: 0.300 AC: 1044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.85
DANN	Benign	0.56

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: rs11175194; hg19: chr12-64264837;