10-43249412-C-G

Position:

• chr10-43249412-C-G

Variant summary

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

The NM_145313.4(RASGEF1A):​c.-7+17433G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,152 control chromosomes in the GnomAD database, including 27,278 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 0.60 (27278 hom., cov: 34)
• Consequence: RASGEF1A NM_145313.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.288

Genes affected

RASGEF1A (HGNC:24246): (RasGEF domain family member 1A) Enables guanyl-nucleotide exchange factor activity. Involved in cell migration and positive regulation of Ras protein signal transduction. Predicted to be located in cytosol. [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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASGEF1A	NM_145313.4	c.-7+17433G>C		intron_variant		ENST00000395810.6	NP_660356.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASGEF1A	ENST00000395810.6	c.-7+17433G>C		intron_variant		1	NM_145313.4	ENSP00000379155	A1

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90659 AN: 152034 Hom.: 27226 Cov.: 34

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.597 AC: 90771 AN: 152152 Hom.: 27278 Cov.: 34 AF XY: 0.598 AC XY: 44492 AN XY: 74368

Gnomad4 AFR AF: 0.676

Gnomad4 AMR AF: 0.610

Gnomad4 ASJ AF: 0.526

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.662

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.580

Alfa AF: 0.567 Hom.: 3073

Bravo AF: 0.599

Asia WGS AF: 0.510 AC: 1776 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2460551; hg19: chr10-43744860; COSMIC: COSV67666474;