chr10-43199601-T-C

Position:

• chr10-43199601-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• 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/exons	MANE	UniProt
RASGEF1A	NM_145313.4	c.849+75A>G		intron_variant		ENST00000395810.6
RASGEF1A	NM_001282862.2	c.873+75A>G		intron_variant
RASGEF1A	XM_005271809.4	c.609+75A>G		intron_variant
RASGEF1A	XM_011539500.3	c.609+75A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASGEF1A	ENST00000395810.6	c.849+75A>G		intron_variant		1	NM_145313.4	A1
RASGEF1A	ENST00000374455.2	c.553+75A>G		intron_variant		5
RASGEF1A	ENST00000374459.5	c.873+75A>G		intron_variant		2		P4
RASGEF1A	ENST00000395809.5	c.849+75A>G		intron_variant		2		A1

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

Gnomad4 AFR exome AF: 0.812

Gnomad4 AMR exome AF: 0.786

Gnomad4 ASJ exome AF: 0.727

Gnomad4 EAS exome AF: 0.932

Gnomad4 SAS exome AF: 0.839

Gnomad4 FIN exome AF: 0.788

Gnomad4 NFE exome AF: 0.703

Gnomad4 OTH exome AF: 0.741

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

Gnomad4 AFR AF: 0.808

Gnomad4 AMR AF: 0.777

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.939

Gnomad4 SAS AF: 0.850

Gnomad4 FIN AF: 0.804

Gnomad4 NFE AF: 0.709

Gnomad4 OTH AF: 0.764

Alfa AF: 0.724 Hom.: 23536

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

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: rs1254964; hg19: chr10-43695049;