rs4567661

Positions:

• chr15-38493913-A-C
• chr15-38493913-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005739.4(RASGRP1):​c.2259+469T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 152,118 control chromosomes in the GnomAD database, including 8,823 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 0.34 (8823 hom., cov: 32)
• Consequence: RASGRP1 NM_005739.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASGRP1	NM_005739.4	c.2259+469T>G		intron_variant		ENST00000310803.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASGRP1	ENST00000310803.10	c.2259+469T>G		intron_variant		1	NM_005739.4	P1
	ENST00000661802.1	n.606A>C		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51220 AN: 152000 Hom.: 8808 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.337 AC: 51278 AN: 152118 Hom.: 8823 Cov.: 32 AF XY: 0.341 AC XY: 25344 AN XY: 74354

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.347

Alfa AF: 0.357 Hom.: 12873

Bravo AF: 0.342

Asia WGS AF: 0.399 AC: 1385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.3
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs4567661; hg19: chr15-38786114;