rs1254967

chr10-43194943-G-Achr10-43194943-G-C

Variant summary

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

The NM_145313.4(RASGEF1A):c.*1301C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,688 control chromosomes in the GnomAD database, including 2,604 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 (2594 hom., cov: 34)
  • Exomes 𝑓: 0.21 (10 hom.)
• Consequence: RASGEF1A NM_145313.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASGEF1A	NM_145313.4	c.*1301C>T		3_prime_UTR_variant	13/13	ENST00000395810.6
RASGEF1A	NM_001282862.2	c.*1301C>T		3_prime_UTR_variant	13/13
RASGEF1A	XM_005271809.4	c.*1301C>T		3_prime_UTR_variant	12/12
RASGEF1A	XM_011539500.3	c.*1301C>T		3_prime_UTR_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASGEF1A	ENST00000395810.6	c.*1301C>T		3_prime_UTR_variant	13/13	1	NM_145313.4	A1
RASGEF1A	ENST00000374459.5	c.*1301C>T		3_prime_UTR_variant	13/13	2		P4

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23637 AN: 152116 Hom.: 2600 Cov.: 34

Gnomad AFR AF: 0.0347

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.172

GnomAD4 exome AF: 0.207 AC: 94 AN: 454 Hom.: 10 Cov.: 0 AF XY: 0.183 AC XY: 53 AN XY: 290

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.224

Gnomad4 NFE exome AF: 0.152

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.155 AC: 23620 AN: 152234 Hom.: 2594 Cov.: 34 AF XY: 0.159 AC XY: 11824 AN XY: 74432

Gnomad4 AFR AF: 0.0346

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.499

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.172

Alfa AF: 0.173 Hom.: 602

Bravo AF: 0.148

Asia WGS AF: 0.372 AC: 1293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	5.8
Dann	Benign	0.66

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: rs1254967; hg19: chr10-43690391;