1-17643083-G-T

Variant names:

• chr1-17643083-G-T
• rs3766306
• NM_018125.4:c.2272+2781G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_018125.4(ARHGEF10L):​c.2272+2781G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,188 control chromosomes in the GnomAD database, including 1,191 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 0.11 (1191 hom., cov: 33)
• Consequence: ARHGEF10L NM_018125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45
• Publications: 4 publications found

Genes affected

ARHGEF10L (HGNC:25540): (Rho guanine nucleotide exchange factor 10 like) This gene belongs to the RhoGEF subfamily of RhoGTPases. Members of this subfamily are activated by specific guanine nucleotide exchange factors (GEFs) and are involved in signal transduction. The encoded protein shows cytosolic distribution. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2016]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF10L	NM_018125.4	c.2272+2781G>T		intron_variant	Intron 21 of 28	ENST00000361221.8	NP_060595.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF10L	ENST00000361221.8	c.2272+2781G>T		intron_variant	Intron 21 of 28	1	NM_018125.4	ENSP00000355060.3

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16833 AN: 152070 Hom.: 1192 Cov.: 33

Gnomad AFR AF: 0.0501

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.0671

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.0605

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.111 AC: 16842 AN: 152188 Hom.: 1191 Cov.: 33 AF XY: 0.109 AC XY: 8143 AN XY: 74404

African (AFR) AF: 0.0502 AC: 2083 AN: 41520

American (AMR) AF: 0.0670 AC: 1025 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 508 AN: 3472

East Asian (EAS) AF: 0.0604 AC: 313 AN: 5182

South Asian (SAS) AF: 0.104 AC: 502 AN: 4824

European-Finnish (FIN) AF: 0.169 AC: 1792 AN: 10590

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10225 AN: 67992

Other (OTH) AF: 0.100 AC: 212 AN: 2114

Alfa AF: 0.123 Hom.: 694

Bravo AF: 0.102

Asia WGS AF: 0.0710 AC: 246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Benign	0.62
PhyloP100		1.5
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: rs3766306; hg19: chr1-17969578;