rs1254958

Positions:

• chr10-43206695-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.-6-573G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 986,606 control chromosomes in the GnomAD database, including 15,455 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 0.16 (2616 hom., cov: 33)
  • Exomes 𝑓: 0.17 (12839 hom.)
• Consequence: RASGEF1A NM_145313.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASGEF1A	NM_145313.4	c.-6-573G>A		intron_variant		ENST00000395810.6
RASGEF1A	NM_001282862.2	c.19-573G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASGEF1A	ENST00000395810.6	c.-6-573G>A		intron_variant		1	NM_145313.4	A1
RASGEF1A	ENST00000395809.5	c.-18G>A		5_prime_UTR_variant	1/13	2		A1
RASGEF1A	ENST00000374459.5	c.19-573G>A		intron_variant		2		P4

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24460 AN: 152004 Hom.: 2622 Cov.: 33

Gnomad AFR AF: 0.0547

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.177

GnomAD4 exome AF: 0.172 AC: 143360 AN: 834484 Hom.: 12839 Cov.: 28 AF XY: 0.172 AC XY: 66381 AN XY: 385478

Gnomad4 AFR exome AF: 0.0436

Gnomad4 AMR exome AF: 0.224

Gnomad4 ASJ exome AF: 0.234

Gnomad4 EAS exome AF: 0.479

Gnomad4 SAS exome AF: 0.253

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.170

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.161 AC: 24443 AN: 152122 Hom.: 2616 Cov.: 33 AF XY: 0.164 AC XY: 12192 AN XY: 74358

Gnomad4 AFR AF: 0.0545

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.177

Alfa AF: 0.181 Hom.: 497

Bravo AF: 0.154

Asia WGS AF: 0.370 AC: 1287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.053
DANN	Benign	0.58

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: rs1254958; hg19: chr10-43702143;