10-43249412-C-G

Variant names:

• chr10-43249412-C-G
• rs2460551
• NM_145313.4:c.-7+17433G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145313.4. 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
	RASGEF1A	NM_145313.4	MANE Select	c.-7+17433G>C		intron	N/A	NP_660356.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGEF1A	ENST00000395810.6	TSL:1 MANE Select	c.-7+17433G>C		intron	N/A	ENSP00000379155.1

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

African (AFR) AF: 0.676 AC: 28066 AN: 41508

American (AMR) AF: 0.610 AC: 9333 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1825 AN: 3472

East Asian (EAS) AF: 0.443 AC: 2292 AN: 5168

South Asian (SAS) AF: 0.558 AC: 2697 AN: 4832

European-Finnish (FIN) AF: 0.662 AC: 6996 AN: 10574

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.553 AC: 37590 AN: 67988

Other (OTH) AF: 0.580 AC: 1226 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.34
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2460551; hg19: chr10-43744860; COSMIC: COSV67666474;