rs10793422

Variant names:

• chr10-43208426-G-A
• rs10793422
• NM_145313.4:c.-6-2304C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-43208426-G-A
• chr10-43208426-G-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.-6-2304C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 985,464 control chromosomes in the GnomAD database, including 15,422 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 0.16 (2616 hom., cov: 33)
  • Exomes 𝑓: 0.17 (12806 hom.)
• Consequence: RASGEF1A NM_145313.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.307
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 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.-6-2304C>T		intron	N/A	NP_660356.2	Q8N9B8-1
	RASGEF1A	NM_001282862.2		c.19-2304C>T		intron	N/A	NP_001269791.1	Q8N9B8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGEF1A	ENST00000395810.6	TSL:1 MANE Select	c.-6-2304C>T		intron	N/A	ENSP00000379155.1	Q8N9B8-1
	RASGEF1A	ENST00000395809.5	TSL:2	c.-1749C>T		5_prime_UTR	Exon 1 of 13	ENSP00000379154.1	Q8N9B8-1
	RASGEF1A	ENST00000954344.1		c.-6-2304C>T		intron	N/A	ENSP00000624403.1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24463 AN: 152068 Hom.: 2622 Cov.: 33

Gnomad AFR AF: 0.0546

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.177

GnomAD4 exome AF: 0.172 AC: 143094 AN: 833278 Hom.: 12806 Cov.: 30 AF XY: 0.172 AC XY: 66247 AN XY: 384848

African (AFR) AF: 0.0434 AC: 686 AN: 15796

American (AMR) AF: 0.230 AC: 226 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 1202 AN: 5154

East Asian (EAS) AF: 0.478 AC: 1740 AN: 3638

South Asian (SAS) AF: 0.253 AC: 4173 AN: 16462

European-Finnish (FIN) AF: 0.151 AC: 43 AN: 284

Middle Eastern (MID) AF: 0.213 AC: 345 AN: 1620

European-Non Finnish (NFE) AF: 0.169 AC: 129137 AN: 762036

Other (OTH) AF: 0.203 AC: 5542 AN: 27304

GnomAD4 genome AF: 0.161 AC: 24446 AN: 152186 Hom.: 2616 Cov.: 33 AF XY: 0.164 AC XY: 12190 AN XY: 74402

African (AFR) AF: 0.0544 AC: 2262 AN: 41552

American (AMR) AF: 0.193 AC: 2951 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 818 AN: 3472

East Asian (EAS) AF: 0.497 AC: 2561 AN: 5152

South Asian (SAS) AF: 0.289 AC: 1393 AN: 4828

European-Finnish (FIN) AF: 0.179 AC: 1893 AN: 10602

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.177 AC: 12059 AN: 67972

Other (OTH) AF: 0.178 AC: 376 AN: 2116

Alfa AF: 0.174 Hom.: 355

Bravo AF: 0.154

Asia WGS AF: 0.371 AC: 1288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.96
DANN	Benign	0.76
PhyloP100		-0.31
Mutation Taster		=296/4	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: rs10793422; hg19: chr10-43703874;