10-43199601-T-G

Variant names:

• chr10-43199601-T-G
• rs1254964
• NM_145313.4:c.849+75A>C

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.849+75A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 33)
• Consequence: RASGEF1A NM_145313.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106
• Publications: 12 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=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASGEF1A	NM_145313.4	c.849+75A>C		intron_variant	Intron 7 of 12	ENST00000395810.6	NP_660356.2
RASGEF1A	NM_001282862.2	c.873+75A>C		intron_variant	Intron 7 of 12		NP_001269791.1
RASGEF1A	XM_005271809.4	c.609+75A>C		intron_variant	Intron 6 of 11		XP_005271866.1
RASGEF1A	XM_011539500.3	c.609+75A>C		intron_variant	Intron 6 of 11		XP_011537802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASGEF1A	ENST00000395810.6	c.849+75A>C		intron_variant	Intron 7 of 12	1	NM_145313.4	ENSP00000379155.1
RASGEF1A	ENST00000374459.5	c.873+75A>C		intron_variant	Intron 7 of 12	2		ENSP00000363583.1
RASGEF1A	ENST00000395809.5	c.849+75A>C		intron_variant	Intron 7 of 12	2		ENSP00000379154.1
RASGEF1A	ENST00000374455.2	c.552+75A>C		intron_variant	Intron 5 of 5	5		ENSP00000363579.2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.0
DANN	Benign	0.77
PhyloP100		0.11

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: rs1254964; hg19: chr10-43695049;