rs11175194

Variant names:

• chr12-63871057-G-A
• rs11175194
• NM_020762.4:c.67+26174G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020762.4(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 NM_020762.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.563
• Publications: 9 publications found

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]

SRGAP1 Gene-Disease associations (from GenCC):

• thyroid cancer, nonmedullary, 2

  Inheritance: AD Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SRGAP1	NM_020762.4	c.67+26174G>A		intron_variant	Intron 1 of 21	ENST00000355086.8	NP_065813.1
SRGAP1	NM_001346201.2	c.67+26174G>A		intron_variant	Intron 1 of 21		NP_001333130.1
SRGAP1	XM_024449096.2	c.67+26174G>A		intron_variant	Intron 1 of 13		XP_024304864.1
SRGAP1	XM_024449097.2	c.67+26174G>A		intron_variant	Intron 1 of 11		XP_024304865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRGAP1	ENST00000355086.8	c.67+26174G>A		intron_variant	Intron 1 of 21	1	NM_020762.4	ENSP00000347198.3
SRGAP1	ENST00000631006.3	c.67+26174G>A		intron_variant	Intron 1 of 21	5		ENSP00000485752.2
SRGAP1	ENST00000537556.1	n.81+26174G>A		intron_variant	Intron 1 of 9	2
SRGAP1	ENST00000695902.1	n.67+26174G>A		intron_variant	Intron 1 of 5			ENSP00000512252.1

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

African (AFR) AF: 0.287 AC: 11914 AN: 41444

American (AMR) AF: 0.150 AC: 2294 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0534 AC: 185 AN: 3464

East Asian (EAS) AF: 0.401 AC: 2068 AN: 5158

South Asian (SAS) AF: 0.214 AC: 1028 AN: 4814

European-Finnish (FIN) AF: 0.176 AC: 1857 AN: 10580

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0584 AC: 3973 AN: 68008

Other (OTH) AF: 0.125 AC: 265 AN: 2116

Alfa AF: 0.0871 Hom.: 4356

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
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11175194; hg19: chr12-64264837;