rs8032939

Variant names:

• chr15-38541832-T-C
• rs8032939
• NM_005739.4:c.221-15428A>G

Variant summary

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

The NM_005739.4(RASGRP1):​c.221-15428A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 151,890 control chromosomes in the GnomAD database, including 15,084 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 0.41 (15084 hom., cov: 31)
• Consequence: RASGRP1 NM_005739.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.775
• Publications: 55 publications found

Genes affected

RASGRP1 (HGNC:9878): (RAS guanyl releasing protein 1) This gene is a member of a family of genes characterized by the presence of a Ras superfamily guanine nucleotide exchange factor (GEF) domain. It functions as a diacylglycerol (DAG)-regulated nucleotide exchange factor specifically activating Ras through the exchange of bound GDP for GTP. It activates the Erk/MAP kinase cascade and regulates T-cells and B-cells development, homeostasis and differentiation. Alternatively spliced transcript variants encoding different isoforms have been identified. Altered expression of the different isoforms of this protein may be a cause of susceptibility to systemic lupus erythematosus (SLE). [provided by RefSeq, Jul 2008]

RASGRP1 Gene-Disease associations (from GenCC):

• immunodeficiency 64

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• autoimmune lymphoproliferative syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASGRP1	NM_005739.4	c.221-15428A>G		intron_variant	Intron 2 of 16	ENST00000310803.10	NP_005730.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASGRP1	ENST00000310803.10	c.221-15428A>G		intron_variant	Intron 2 of 16	1	NM_005739.4	ENSP00000310244.5

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61501 AN: 151770 Hom.: 15050 Cov.: 31

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.405 AC: 61590 AN: 151890 Hom.: 15084 Cov.: 31 AF XY: 0.406 AC XY: 30135 AN XY: 74218

African (AFR) AF: 0.678 AC: 28042 AN: 41376

American (AMR) AF: 0.412 AC: 6287 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 957 AN: 3466

East Asian (EAS) AF: 0.589 AC: 3039 AN: 5156

South Asian (SAS) AF: 0.364 AC: 1750 AN: 4814

European-Finnish (FIN) AF: 0.287 AC: 3021 AN: 10534

Middle Eastern (MID) AF: 0.325 AC: 95 AN: 292

European-Non Finnish (NFE) AF: 0.256 AC: 17374 AN: 67964

Other (OTH) AF: 0.380 AC: 804 AN: 2114

Alfa AF: 0.335 Hom.: 17443

Bravo AF: 0.425

Asia WGS AF: 0.476 AC: 1654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.56
DANN	Benign	0.49
PhyloP100		-0.78
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: rs8032939; hg19: chr15-38834033;