10-43235346-T-G

Variant names:

• chr10-43235346-T-G
• rs2503846
• NM_145313.4:c.-6-29224A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145313.4(RASGEF1A):​c.-6-29224A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 152,114 control chromosomes in the GnomAD database, including 44,866 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 0.77 (44866 hom., cov: 32)
• Consequence: RASGEF1A NM_145313.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.385
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145313.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGEF1A	NM_145313.4	MANE Select	c.-6-29224A>C		intron	N/A	NP_660356.2	Q8N9B8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGEF1A	ENST00000395810.6	TSL:1 MANE Select	c.-6-29224A>C		intron	N/A	ENSP00000379155.1	Q8N9B8-1
	RASGEF1A	ENST00000954344.1		c.-6-29224A>C		intron	N/A	ENSP00000624403.1
	RASGEF1A	ENST00000898232.1		c.-6-29224A>C		intron	N/A	ENSP00000568291.1

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116461 AN: 151996 Hom.: 44816 Cov.: 32

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.843

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.767

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

GnomAD4 genome AF: 0.766 AC: 116566 AN: 152114 Hom.: 44866 Cov.: 32 AF XY: 0.772 AC XY: 57378 AN XY: 74352

African (AFR) AF: 0.758 AC: 31448 AN: 41492

American (AMR) AF: 0.804 AC: 12299 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2687 AN: 3468

East Asian (EAS) AF: 0.957 AC: 4940 AN: 5164

South Asian (SAS) AF: 0.855 AC: 4119 AN: 4818

European-Finnish (FIN) AF: 0.843 AC: 8929 AN: 10590

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.730 AC: 49628 AN: 67974

Other (OTH) AF: 0.769 AC: 1626 AN: 2114

Alfa AF: 0.744 Hom.: 177977

Bravo AF: 0.762

Asia WGS AF: 0.889 AC: 3090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.4
DANN	Benign	0.47
PhyloP100		0.39
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: rs2503846; hg19: chr10-43730794;