rs1822818

chr4-81541443-T-C

Variant summary

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

The ENST00000638048.1(RASGEF1B):c.255+61396A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 151,788 control chromosomes in the GnomAD database, including 2,644 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 0.18 (2644 hom., cov: 31)
• Consequence: RASGEF1B ENST00000638048.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.820

Genes affected

RASGEF1B (HGNC:24881): (RasGEF domain family member 1B) Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity and small GTPase mediated signal transduction. Predicted to be located in early endosome; late endosome; and midbody. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASGEF1B	ENST00000638048.1	c.255+61396A>G		intron_variant		5
RASGEF1B	ENST00000512716.1	c.172-19898A>G		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27049 AN: 151670 Hom.: 2645 Cov.: 31

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.0958

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.208

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.178 AC: 27061 AN: 151788 Hom.: 2644 Cov.: 31 AF XY: 0.179 AC XY: 13280 AN XY: 74168

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.0958

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.198

Alfa AF: 0.160 Hom.: 980

Bravo AF: 0.192

Asia WGS AF: 0.141 AC: 491 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	7.3
Dann	Benign	0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1822818; hg19: chr4-82462597;