rs7971621

Variant names:

• chr12-63866834-G-A
• rs7971621
• NM_020762.4:c.67+21951G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-63866834-G-A
• chr12-63866834-G-C
• chr12-63866834-G-T

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+21951G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.971 in 151,588 control chromosomes in the GnomAD database, including 71,528 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 0.97 (71528 hom., cov: 27)
• Consequence: SRGAP1 NM_020762.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.699
• Publications: 1 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):

• congenital anomaly of kidney and urinary tract

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.983 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020762.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRGAP1	NM_020762.4	MANE Select	c.67+21951G>A		intron	N/A	NP_065813.1	Q7Z6B7-1
	SRGAP1	NM_001346201.2		c.67+21951G>A		intron	N/A	NP_001333130.1	Q7Z6B7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRGAP1	ENST00000355086.8	TSL:1 MANE Select	c.67+21951G>A		intron	N/A	ENSP00000347198.3	Q7Z6B7-1
	SRGAP1	ENST00000875666.1		c.67+21951G>A		intron	N/A	ENSP00000545725.1
	SRGAP1	ENST00000631006.3	TSL:5	c.67+21951G>A		intron	N/A	ENSP00000485752.2	Q7Z6B7-2

Frequencies

GnomAD3 genomes AF: 0.971 AC: 147110 AN: 151476 Hom.: 71473 Cov.: 27

Gnomad AFR AF: 0.991

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.987

Gnomad ASJ AF: 0.986

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.971

Gnomad FIN AF: 0.981

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.951

Gnomad OTH AF: 0.978

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

GnomAD4 genome AF: 0.971 AC: 147221 AN: 151588 Hom.: 71528 Cov.: 27 AF XY: 0.973 AC XY: 72071 AN XY: 74044

African (AFR) AF: 0.991 AC: 40973 AN: 41326

American (AMR) AF: 0.987 AC: 15030 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.986 AC: 3419 AN: 3468

East Asian (EAS) AF: 0.999 AC: 5173 AN: 5176

South Asian (SAS) AF: 0.971 AC: 4646 AN: 4784

European-Finnish (FIN) AF: 0.981 AC: 10177 AN: 10378

Middle Eastern (MID) AF: 1.00 AC: 292 AN: 292

European-Non Finnish (NFE) AF: 0.951 AC: 64619 AN: 67922

Other (OTH) AF: 0.978 AC: 2062 AN: 2108

Alfa AF: 0.959 Hom.: 14197

Bravo AF: 0.973

Asia WGS AF: 0.986 AC: 3429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.75
DANN	Benign	0.17
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7971621; hg19: chr12-64260614;