4-81620874-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASGEF1B	ENST00000638048.1	c.172-17952G>A		intron_variant	Intron 3 of 16	5		ENSP00000490436.1
RASGEF1B	ENST00000514050.6	c.172-17952G>A		intron_variant	Intron 3 of 3	2		ENSP00000490814.1
RASGEF1B	ENST00000510780.5	n.490+14924G>A		intron_variant	Intron 5 of 5	3

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

Gnomad4 AFR AF: 0.790

Gnomad4 AMR AF: 0.979

Gnomad4 ASJ AF: 0.975

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.958

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 v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4382026; hg19: chr4-82542028;