10-43239327-T-C

Variant names:

• chr10-43239327-T-C
• rs1879310
• NM_145313.4:c.-7+27518A>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+27518A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,228 control chromosomes in the GnomAD database, including 2,781 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 0.17 (2781 hom., cov: 33)
• Consequence: RASGEF1A NM_145313.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.598

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASGEF1A	NM_145313.4	c.-7+27518A>G		intron_variant	Intron 1 of 12	ENST00000395810.6	NP_660356.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASGEF1A	ENST00000395810.6	c.-7+27518A>G		intron_variant	Intron 1 of 12	1	NM_145313.4	ENSP00000379155.1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25590 AN: 152110 Hom.: 2787 Cov.: 33

Gnomad AFR AF: 0.0733

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.168 AC: 25575 AN: 152228 Hom.: 2781 Cov.: 33 AF XY: 0.171 AC XY: 12744 AN XY: 74420

Gnomad4 AFR AF: 0.0731

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.188

Alfa AF: 0.187 Hom.: 670

Bravo AF: 0.162

Asia WGS AF: 0.376 AC: 1305 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.1
DANN	Benign	0.73

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: rs1879310; hg19: chr10-43734775;