rs7177101

Variant names:

• chr15-38507168-G-A
• rs7177101
• NM_005739.4:c.1242+558C>T

Variant summary

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

The NM_005739.4(RASGRP1):​c.1242+558C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 151,986 control chromosomes in the GnomAD database, including 15,441 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 0.44 (15441 hom., cov: 32)
• Consequence: RASGRP1 NM_005739.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.489
• Publications: 11 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

LOC105370774 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASGRP1	NM_005739.4	c.1242+558C>T		intron_variant	Intron 9 of 16	ENST00000310803.10	NP_005730.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASGRP1	ENST00000310803.10	c.1242+558C>T		intron_variant	Intron 9 of 16	1	NM_005739.4	ENSP00000310244.5

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66689 AN: 151868 Hom.: 15397 Cov.: 32

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.439 AC: 66789 AN: 151986 Hom.: 15441 Cov.: 32 AF XY: 0.445 AC XY: 33053 AN XY: 74280

African (AFR) AF: 0.546 AC: 22612 AN: 41434

American (AMR) AF: 0.442 AC: 6755 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1114 AN: 3470

East Asian (EAS) AF: 0.692 AC: 3576 AN: 5170

South Asian (SAS) AF: 0.610 AC: 2939 AN: 4820

European-Finnish (FIN) AF: 0.408 AC: 4307 AN: 10544

Middle Eastern (MID) AF: 0.363 AC: 106 AN: 292

European-Non Finnish (NFE) AF: 0.355 AC: 24102 AN: 67954

Other (OTH) AF: 0.407 AC: 861 AN: 2114

Alfa AF: 0.378 Hom.: 49331

Bravo AF: 0.442

Asia WGS AF: 0.631 AC: 2191 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	5.5
DANN	Benign	0.35
PhyloP100		0.49
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: rs7177101; hg19: chr15-38799369;