rs7090455

chr10-43258084-C-T

Variant summary

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

The NM_145313.4(RASGEF1A):c.-7+8761G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,286 control chromosomes in the GnomAD database, including 2,358 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 0.14 (2358 hom., cov: 34)
• Consequence: RASGEF1A NM_145313.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASGEF1A	NM_145313.4	c.-7+8761G>A		intron_variant		ENST00000395810.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASGEF1A	ENST00000395810.6	c.-7+8761G>A		intron_variant		1	NM_145313.4	A1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21539 AN: 152168 Hom.: 2362 Cov.: 34

Gnomad AFR AF: 0.0406

Gnomad AMI AF: 0.0912

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.141 AC: 21533 AN: 152286 Hom.: 2358 Cov.: 34 AF XY: 0.147 AC XY: 10975 AN XY: 74462

Gnomad4 AFR AF: 0.0405

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.168

Alfa AF: 0.161 Hom.: 635

Bravo AF: 0.142

Asia WGS AF: 0.381 AC: 1322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	1.8
Dann	Benign	0.36

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: rs7090455; hg19: chr10-43753532;