10-43194943-G-T

Variant names:

• chr10-43194943-G-T
• rs1254967
• NM_145313.4:c.*1301C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145313.4(RASGEF1A):​c.*1301C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0022 in 454 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0022 (0 hom.)
• Consequence: RASGEF1A NM_145313.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASGEF1A	NM_145313.4	c.*1301C>A		3_prime_UTR_variant	Exon 13 of 13	ENST00000395810.6	NP_660356.2
RASGEF1A	NM_001282862.2	c.*1301C>A		3_prime_UTR_variant	Exon 13 of 13		NP_001269791.1
RASGEF1A	XM_005271809.4	c.*1301C>A		3_prime_UTR_variant	Exon 12 of 12		XP_005271866.1
RASGEF1A	XM_011539500.3	c.*1301C>A		3_prime_UTR_variant	Exon 12 of 12		XP_011537802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASGEF1A	ENST00000395810.6	c.*1301C>A		3_prime_UTR_variant	Exon 13 of 13	1	NM_145313.4	ENSP00000379155.1
RASGEF1A	ENST00000374459.5	c.*1301C>A		3_prime_UTR_variant	Exon 13 of 13	2		ENSP00000363583.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00220 AC: 1 AN: 454 Hom.: 0 Cov.: 0 AF XY: 0.00345 AC XY: 1 AN XY: 290

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.0109 AC: 1 AN: 92

Other (OTH) AF: 0.00 AC: 0 AN: 4

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.70
PhyloP100		0.21

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: rs1254967; hg19: chr10-43690391;