rs1822818

Variant names:

• chr4-81541443-T-C
• rs1822818
• ENST00000638048.1:c.255+61396A>G

Variant summary

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

The ENST00000512716.1(RASGEF1B):​n.172-19898A>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 ENST00000512716.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.820
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000512716.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGEF1B	ENST00000638048.1	TSL:5	c.255+61396A>G		intron	N/A	ENSP00000490436.1
	RASGEF1B	ENST00000512716.1	TSL:3	n.172-19898A>G		intron	N/A	ENSP00000476065.2

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

African (AFR) AF: 0.200 AC: 8278 AN: 41360

American (AMR) AF: 0.287 AC: 4372 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 758 AN: 3468

East Asian (EAS) AF: 0.0958 AC: 493 AN: 5144

South Asian (SAS) AF: 0.172 AC: 829 AN: 4810

European-Finnish (FIN) AF: 0.154 AC: 1622 AN: 10520

Middle Eastern (MID) AF: 0.200 AC: 58 AN: 290

European-Non Finnish (NFE) AF: 0.150 AC: 10164 AN: 67952

Other (OTH) AF: 0.198 AC: 418 AN: 2114

Alfa AF: 0.167 Hom.: 1389

Bravo AF: 0.192

Asia WGS AF: 0.141 AC: 491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.3
DANN	Benign	0.42
PhyloP100		0.82

Splicing

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

Other links and lift over

dbSNP: rs1822818; hg19: chr4-82462597;