rs11175219

Positions:

• chr12-63968939-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_020762.4(SRGAP1):​c.68-15008C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0797 in 152,186 control chromosomes in the GnomAD database, including 636 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 0.080 (636 hom., cov: 32)
• Consequence: SRGAP1 NM_020762.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.422

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRGAP1	NM_020762.4	c.68-15008C>T		intron_variant		ENST00000355086.8	NP_065813.1
SRGAP1	NM_001346201.2	c.68-15008C>T		intron_variant			NP_001333130.1
SRGAP1	XM_024449096.2	c.68-15008C>T		intron_variant			XP_024304864.1
SRGAP1	XM_024449097.2	c.68-15008C>T		intron_variant			XP_024304865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRGAP1	ENST00000355086.8	c.68-15008C>T		intron_variant		1	NM_020762.4	ENSP00000347198	A1
SRGAP1	ENST00000631006.3	c.68-15008C>T		intron_variant		5		ENSP00000485752	P3
SRGAP1	ENST00000695902.1	c.222-15008C>T		intron_variant, NMD_transcript_variant				ENSP00000512252
SRGAP1	ENST00000537556.1	n.82-15008C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0796 AC: 12111 AN: 152068 Hom.: 633 Cov.: 32

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0492

Gnomad ASJ AF: 0.0577

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0487

Gnomad FIN AF: 0.0653

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.0714

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

GnomAD4 genome AF: 0.0797 AC: 12122 AN: 152186 Hom.: 636 Cov.: 32 AF XY: 0.0751 AC XY: 5584 AN XY: 74390

Gnomad4 AFR AF: 0.0221

Gnomad4 AMR AF: 0.0491

Gnomad4 ASJ AF: 0.0577

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.0489

Gnomad4 FIN AF: 0.0653

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.0773

Alfa AF: 0.105 Hom.: 1275

Bravo AF: 0.0751

Asia WGS AF: 0.0820 AC: 285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	17
DANN	Benign	0.69

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: rs11175219; hg19: chr12-64362719;