chr5-180161797-C-T

Position:

• chr5-180161797-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
RASGEF1C	NM_175062.4	c.-6-23739G>A		intron_variant		ENST00000361132.9	NP_778232.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASGEF1C	ENST00000361132.9	c.-6-23739G>A		intron_variant		1	NM_175062.4	ENSP00000354963	P1
RASGEF1C	ENST00000615330.4	c.-459-23739G>A		intron_variant		5		ENSP00000481349

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

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.0864

Gnomad4 ASJ AF: 0.0832

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.125

Alfa AF: 0.140 Hom.: 2431

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs10068846; hg19: chr5-179588797;