chr12-63939865-G-A

Variant names:

• chr12-63939865-G-A
• rs7973936
• NM_020762.4:c.68-44082G>A

Variant summary

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

The NM_020762.4(SRGAP1):​c.68-44082G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 151,986 control chromosomes in the GnomAD database, including 7,109 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 0.30 (7109 hom., cov: 30)
• Consequence: SRGAP1 NM_020762.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRGAP1	NM_020762.4	c.68-44082G>A		intron_variant	Intron 1 of 21	ENST00000355086.8	NP_065813.1
SRGAP1	NM_001346201.2	c.68-44082G>A		intron_variant	Intron 1 of 21		NP_001333130.1
SRGAP1	XM_024449096.2	c.68-44082G>A		intron_variant	Intron 1 of 13		XP_024304864.1
SRGAP1	XM_024449097.2	c.68-44082G>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.68-44082G>A		intron_variant	Intron 1 of 21	1	NM_020762.4	ENSP00000347198.3
SRGAP1	ENST00000631006.3	c.68-44082G>A		intron_variant	Intron 1 of 21	5		ENSP00000485752.2
SRGAP1	ENST00000537556.1	n.82-44082G>A		intron_variant	Intron 1 of 9	2
SRGAP1	ENST00000695902.1	n.221+1867G>A		intron_variant	Intron 2 of 5			ENSP00000512252.1

Frequencies

GnomAD3 genomes AF: 0.296 AC: 45027 AN: 151868 Hom.: 7105 Cov.: 30

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.296 AC: 45029 AN: 151986 Hom.: 7109 Cov.: 30 AF XY: 0.302 AC XY: 22425 AN XY: 74300

African (AFR) AF: 0.186 AC: 7707 AN: 41480

American (AMR) AF: 0.363 AC: 5537 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1098 AN: 3466

East Asian (EAS) AF: 0.517 AC: 2664 AN: 5156

South Asian (SAS) AF: 0.370 AC: 1781 AN: 4820

European-Finnish (FIN) AF: 0.345 AC: 3644 AN: 10550

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21601 AN: 67924

Other (OTH) AF: 0.321 AC: 679 AN: 2112

Alfa AF: 0.287 Hom.: 3562

Bravo AF: 0.296

Asia WGS AF: 0.396 AC: 1375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.14
DANN	Benign	0.29
PhyloP100		-1.1
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: rs7973936; hg19: chr12-64333645;