chr10-43194943-G-A

Variant names:

• chr10-43194943-G-A
• rs1254967
• NM_145313.4:c.*1301C>T

Variant summary

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

The NM_145313.4(RASGEF1A):​c.*1301C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,688 control chromosomes in the GnomAD database, including 2,604 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 (2594 hom., cov: 34)
  • Exomes 𝑓: 0.21 (10 hom.)
• Consequence: RASGEF1A NM_145313.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.483 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.*1301C>T		3_prime_UTR	Exon 13 of 13	NP_660356.2
	RASGEF1A	NM_001282862.2		c.*1301C>T		3_prime_UTR	Exon 13 of 13	NP_001269791.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGEF1A	ENST00000395810.6	TSL:1 MANE Select	c.*1301C>T		3_prime_UTR	Exon 13 of 13	ENSP00000379155.1
	RASGEF1A	ENST00000374459.5	TSL:2	c.*1301C>T		3_prime_UTR	Exon 13 of 13	ENSP00000363583.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23637 AN: 152116 Hom.: 2600 Cov.: 34

Gnomad AFR AF: 0.0347

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.172

GnomAD4 exome AF: 0.207 AC: 94 AN: 454 Hom.: 10 Cov.: 0 AF XY: 0.183 AC XY: 53 AN XY: 290

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.224 AC: 77 AN: 344

Middle Eastern (MID) AF: 0.250 AC: 1 AN: 4

European-Non Finnish (NFE) AF: 0.152 AC: 14 AN: 92

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.155 AC: 23620 AN: 152234 Hom.: 2594 Cov.: 34 AF XY: 0.159 AC XY: 11824 AN XY: 74432

African (AFR) AF: 0.0346 AC: 1436 AN: 41562

American (AMR) AF: 0.191 AC: 2927 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 818 AN: 3468

East Asian (EAS) AF: 0.499 AC: 2581 AN: 5170

South Asian (SAS) AF: 0.289 AC: 1394 AN: 4826

European-Finnish (FIN) AF: 0.179 AC: 1896 AN: 10604

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12067 AN: 67988

Other (OTH) AF: 0.172 AC: 365 AN: 2116

Alfa AF: 0.166 Hom.: 657

Bravo AF: 0.148

Asia WGS AF: 0.372 AC: 1293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.8
DANN	Benign	0.66
PhyloP100		0.21
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: rs1254967; hg19: chr10-43690391;