chr5-180161797-C-T

Variant names:

• chr5-180161797-C-T
• rs10068846
• NM_175062.4:c.-6-23739G>A

Variant summary

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

The NM_175062.4(RASGEF1C):​c.-6-23739G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,258 control chromosomes in the GnomAD database, including 1,948 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 0.15 (1948 hom., cov: 34)
• Consequence: RASGEF1C NM_175062.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• Publications: 5 publications found

Genes affected

RASGEF1C (HGNC:27400): (RasGEF domain family member 1C) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity and small GTPase mediated signal transduction. [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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASGEF1C	NM_175062.4	c.-6-23739G>A		intron_variant	Intron 1 of 13	ENST00000361132.9	NP_778232.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASGEF1C	ENST00000361132.9	c.-6-23739G>A		intron_variant	Intron 1 of 13	1	NM_175062.4	ENSP00000354963.4
RASGEF1C	ENST00000615330.4	c.-459-23739G>A		intron_variant	Intron 1 of 14	5		ENSP00000481349.1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23444 AN: 152140 Hom.: 1949 Cov.: 34

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.0866

Gnomad ASJ AF: 0.0832

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.154 AC: 23454 AN: 152258 Hom.: 1948 Cov.: 34 AF XY: 0.156 AC XY: 11578 AN XY: 74434

African (AFR) AF: 0.182 AC: 7544 AN: 41554

American (AMR) AF: 0.0864 AC: 1323 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0832 AC: 289 AN: 3472

East Asian (EAS) AF: 0.165 AC: 850 AN: 5166

South Asian (SAS) AF: 0.123 AC: 594 AN: 4832

European-Finnish (FIN) AF: 0.200 AC: 2126 AN: 10604

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10306 AN: 68010

Other (OTH) AF: 0.125 AC: 264 AN: 2108

Alfa AF: 0.144 Hom.: 5752

Bravo AF: 0.148

Asia WGS AF: 0.122 AC: 424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.57
DANN	Benign	0.90
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10068846; hg19: chr5-179588797;