5-81074953-A-C

Variant names:

• chr5-81074953-A-C
• rs11741062
• NM_006909.3:c.887+1501A>C

Variant summary

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

The NM_006909.3(RASGRF2):​c.887+1501A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,108 control chromosomes in the GnomAD database, including 2,268 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 0.15 (2268 hom., cov: 32)
• Consequence: RASGRF2 NM_006909.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500
• Publications: 2 publications found

Genes affected

RASGRF2 (HGNC:9876): (Ras protein specific guanine nucleotide releasing factor 2) RAS GTPases cycle between an inactive GDP-bound state and an active GTP-bound state. This gene encodes a calcium-regulated nucleotide exchange factor activating both RAS and RAS-related protein, RAC1, through the exchange of bound GDP for GTP, thereby, coordinating the signaling of distinct mitogen-activated protein kinase pathways. [provided by RefSeq, Oct 2011]

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 = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASGRF2	NM_006909.3	c.887+1501A>C		intron_variant	Intron 5 of 26	ENST00000265080.9	NP_008840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASGRF2	ENST00000265080.9	c.887+1501A>C		intron_variant	Intron 5 of 26	1	NM_006909.3	ENSP00000265080.4
RASGRF2	ENST00000503795.1	n.887+1501A>C		intron_variant	Intron 5 of 27	1		ENSP00000421771.1
RASGRF2	ENST00000638442.1	c.887+1501A>C		intron_variant	Intron 5 of 9	5		ENSP00000491428.1
RASGRF2	ENST00000502677.1	n.812+1501A>C		intron_variant	Intron 2 of 6	2

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23265 AN: 151990 Hom.: 2266 Cov.: 32

Gnomad AFR AF: 0.0843

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0781

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.153 AC: 23273 AN: 152108 Hom.: 2268 Cov.: 32 AF XY: 0.159 AC XY: 11792 AN XY: 74338

African (AFR) AF: 0.0842 AC: 3497 AN: 41528

American (AMR) AF: 0.108 AC: 1657 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0781 AC: 271 AN: 3470

East Asian (EAS) AF: 0.427 AC: 2203 AN: 5154

South Asian (SAS) AF: 0.182 AC: 874 AN: 4800

European-Finnish (FIN) AF: 0.272 AC: 2881 AN: 10574

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11396 AN: 67980

Other (OTH) AF: 0.138 AC: 292 AN: 2110

Alfa AF: 0.161 Hom.: 3766

Bravo AF: 0.139

Asia WGS AF: 0.262 AC: 909 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	1.5
DANN	Benign	0.83
PhyloP100		-0.050
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: rs11741062; hg19: chr5-80370772;