10-43199601-T-C

Variant names:

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

Variant summary

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

The NM_145313.4(RASGEF1A):​c.849+75A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 1,223,124 control chromosomes in the GnomAD database, including 334,250 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 0.76 (44577 hom., cov: 33)
  • Exomes 𝑓: 0.73 (289673 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASGEF1A	NM_145313.4	c.849+75A>G		intron_variant	Intron 7 of 12	ENST00000395810.6	NP_660356.2
RASGEF1A	NM_001282862.2	c.873+75A>G		intron_variant	Intron 7 of 12		NP_001269791.1
RASGEF1A	XM_005271809.4	c.609+75A>G		intron_variant	Intron 6 of 11		XP_005271866.1
RASGEF1A	XM_011539500.3	c.609+75A>G		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>G		intron_variant	Intron 7 of 12	1	NM_145313.4	ENSP00000379155.1
RASGEF1A	ENST00000374459.5	c.873+75A>G		intron_variant	Intron 7 of 12	2		ENSP00000363583.1
RASGEF1A	ENST00000395809.5	c.849+75A>G		intron_variant	Intron 7 of 12	2		ENSP00000379154.1
RASGEF1A	ENST00000374455.2	c.552+75A>G		intron_variant	Intron 5 of 5	5		ENSP00000363579.2

Frequencies

GnomAD3 genomes AF: 0.763 AC: 116032 AN: 152080 Hom.: 44522 Cov.: 33

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.939

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.804

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.762

GnomAD4 exome AF: 0.733 AC: 784991 AN: 1070926 Hom.: 289673 AF XY: 0.736 AC XY: 403392 AN XY: 547806

African (AFR) AF: 0.812 AC: 21196 AN: 26110

American (AMR) AF: 0.786 AC: 32291 AN: 41062

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 17023 AN: 23410

East Asian (EAS) AF: 0.932 AC: 34810 AN: 37332

South Asian (SAS) AF: 0.839 AC: 64425 AN: 76778

European-Finnish (FIN) AF: 0.788 AC: 34996 AN: 44432

Middle Eastern (MID) AF: 0.820 AC: 4189 AN: 5110

European-Non Finnish (NFE) AF: 0.703 AC: 540611 AN: 768880

Other (OTH) AF: 0.741 AC: 35450 AN: 47812

GnomAD4 genome AF: 0.763 AC: 116148 AN: 152198 Hom.: 44577 Cov.: 33 AF XY: 0.769 AC XY: 57245 AN XY: 74394

African (AFR) AF: 0.808 AC: 33573 AN: 41536

American (AMR) AF: 0.777 AC: 11882 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2559 AN: 3470

East Asian (EAS) AF: 0.939 AC: 4842 AN: 5158

South Asian (SAS) AF: 0.850 AC: 4099 AN: 4822

European-Finnish (FIN) AF: 0.804 AC: 8517 AN: 10592

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.709 AC: 48195 AN: 68002

Other (OTH) AF: 0.764 AC: 1617 AN: 2116

Alfa AF: 0.722 Hom.: 34672

Bravo AF: 0.761

Asia WGS AF: 0.879 AC: 3055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.3
DANN	Benign	0.80
PhyloP100		0.11
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: rs1254964; hg19: chr10-43695049;