chr4-81620874-C-T

Variant names:

• chr4-81620874-C-T
• rs4382026
• ENST00000638048.1:c.172-17952G>A

Variant summary

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

The ENST00000514050.6(RASGEF1B):​c.172-17952G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.939 in 152,116 control chromosomes in the GnomAD database, including 67,707 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 0.94 (67707 hom., cov: 31)
• Consequence: RASGEF1B ENST00000514050.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000514050.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGEF1B	ENST00000638048.1	TSL:5	c.172-17952G>A		intron	N/A	ENSP00000490436.1	A0A1B0GVA7
	RASGEF1B	ENST00000514050.6	TSL:2	c.172-17952G>A		intron	N/A	ENSP00000490814.1	A0A1B0GW78
	RASGEF1B	ENST00000510780.5	TSL:3	n.490+14924G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.939 AC: 142750 AN: 151998 Hom.: 67675 Cov.: 31

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.979

Gnomad ASJ AF: 0.975

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.998

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.957

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

GnomAD4 genome AF: 0.939 AC: 142833 AN: 152116 Hom.: 67707 Cov.: 31 AF XY: 0.942 AC XY: 70065 AN XY: 74392

African (AFR) AF: 0.790 AC: 32728 AN: 41424

American (AMR) AF: 0.979 AC: 14944 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.975 AC: 3385 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5188 AN: 5188

South Asian (SAS) AF: 0.999 AC: 4810 AN: 4816

European-Finnish (FIN) AF: 1.00 AC: 10605 AN: 10606

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67945 AN: 68026

Other (OTH) AF: 0.958 AC: 2027 AN: 2116

Alfa AF: 0.971 Hom.: 16746

Bravo AF: 0.931

Asia WGS AF: 0.986 AC: 3427 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.076
DANN	Benign	0.22
PhyloP100		-1.8

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4382026;

hg19: chr4-82542028;