10-43244619-A-G

Variant names:

• chr10-43244619-A-G
• rs7093409
• NM_145313.4:c.-7+22226T>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.-7+22226T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 142,718 control chromosomes in the GnomAD database, including 3,761 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 0.18 (3761 hom., cov: 32)
• Consequence: RASGEF1A NM_145313.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164
• Publications: 10 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGEF1A	NM_145313.4	MANE Select	c.-7+22226T>C		intron	N/A	NP_660356.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGEF1A	ENST00000395810.6	TSL:1 MANE Select	c.-7+22226T>C		intron	N/A	ENSP00000379155.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 26291 AN: 142626 Hom.: 3768 Cov.: 32

Gnomad AFR AF: 0.0787

Gnomad AMI AF: 0.0992

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.184 AC: 26275 AN: 142718 Hom.: 3761 Cov.: 32 AF XY: 0.188 AC XY: 13113 AN XY: 69874

African (AFR) AF: 0.0786 AC: 3103 AN: 39466

American (AMR) AF: 0.212 AC: 3077 AN: 14498

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 910 AN: 3266

East Asian (EAS) AF: 0.511 AC: 2632 AN: 5154

South Asian (SAS) AF: 0.345 AC: 1490 AN: 4316

European-Finnish (FIN) AF: 0.197 AC: 1962 AN: 9978

Middle Eastern (MID) AF: 0.252 AC: 68 AN: 270

European-Non Finnish (NFE) AF: 0.199 AC: 12547 AN: 63030

Other (OTH) AF: 0.209 AC: 408 AN: 1954

Alfa AF: 0.175 Hom.: 6232

Bravo AF: 0.168

Asia WGS AF: 0.383 AC: 1328 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.8
DANN	Benign	0.90
PhyloP100		0.16
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: rs7093409; hg19: chr10-43740067;