chr10-43258084-C-T

Variant names:

• chr10-43258084-C-T
• rs7090455
• NM_145313.4:c.-7+8761G>A

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+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
• Publications: 3 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=-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 rank	MANE	Protein	UniProt
RASGEF1A	NM_145313.4	c.-7+8761G>A		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+8761G>A		intron_variant	Intron 1 of 12	1	NM_145313.4	ENSP00000379155.1

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

African (AFR) AF: 0.0405 AC: 1685 AN: 41576

American (AMR) AF: 0.237 AC: 3623 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 649 AN: 3472

East Asian (EAS) AF: 0.528 AC: 2730 AN: 5166

South Asian (SAS) AF: 0.281 AC: 1357 AN: 4828

European-Finnish (FIN) AF: 0.137 AC: 1450 AN: 10622

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9536 AN: 68006

Other (OTH) AF: 0.168 AC: 354 AN: 2112

Alfa AF: 0.168 Hom.: 1278

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
PhyloP100		-1.5
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: rs7090455; hg19: chr10-43753532;