chr5-180158240-A-G

Variant names:

• chr5-180158240-A-G
• rs10079475
• NM_175062.4:c.-6-20182T>C

Variant summary

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

The NM_175062.4(RASGEF1C):​c.-6-20182T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,130 control chromosomes in the GnomAD database, including 1,850 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 (1850 hom., cov: 32)
• Consequence: RASGEF1C NM_175062.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175062.4. 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
	RASGEF1C	NM_175062.4	MANE Select	c.-6-20182T>C		intron	N/A	NP_778232.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASGEF1C	ENST00000361132.9	TSL:1 MANE Select	c.-6-20182T>C		intron	N/A	ENSP00000354963.4	Q8N431-1
	RASGEF1C	ENST00000923269.1		c.-6-20182T>C		intron	N/A	ENSP00000593328.1
	RASGEF1C	ENST00000967585.1		c.-2-20186T>C		intron	N/A	ENSP00000637644.1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22858 AN: 152010 Hom.: 1849 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.0892

Gnomad ASJ AF: 0.0836

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.150 AC: 22872 AN: 152130 Hom.: 1850 Cov.: 32 AF XY: 0.151 AC XY: 11221 AN XY: 74352

African (AFR) AF: 0.169 AC: 6999 AN: 41492

American (AMR) AF: 0.0890 AC: 1362 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0836 AC: 290 AN: 3468

East Asian (EAS) AF: 0.177 AC: 918 AN: 5174

South Asian (SAS) AF: 0.104 AC: 500 AN: 4824

European-Finnish (FIN) AF: 0.203 AC: 2140 AN: 10564

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10255 AN: 67994

Other (OTH) AF: 0.121 AC: 256 AN: 2110

Alfa AF: 0.141 Hom.: 600

Bravo AF: 0.143

Asia WGS AF: 0.124 AC: 433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.6
DANN	Benign	0.38
PhyloP100		0.090
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: rs10079475; hg19: chr5-179585240;