rs6693036

Positions:

• chr1-17593322-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018125.4(ARHGEF10L):​c.257+4843T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0977 in 152,248 control chromosomes in the GnomAD database, including 1,173 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 0.098 (1173 hom., cov: 32)
• Consequence: ARHGEF10L NM_018125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF10L	NM_018125.4	c.257+4843T>C		intron_variant		ENST00000361221.8	NP_060595.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF10L	ENST00000361221.8	c.257+4843T>C		intron_variant		1	NM_018125.4	ENSP00000355060	A1
ARHGEF10L	ENST00000375415.5	c.257+4843T>C		intron_variant		1		ENSP00000364564	P4

Frequencies

GnomAD3 genomes AF: 0.0976 AC: 14850 AN: 152130 Hom.: 1170 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.0870

Gnomad AMR AF: 0.0568

Gnomad ASJ AF: 0.0476

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.0348

Gnomad FIN AF: 0.0403

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0442

Gnomad OTH AF: 0.0855

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

GnomAD4 genome AF: 0.0977 AC: 14869 AN: 152248 Hom.: 1173 Cov.: 32 AF XY: 0.0963 AC XY: 7165 AN XY: 74440

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.0568

Gnomad4 ASJ AF: 0.0476

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.0348

Gnomad4 FIN AF: 0.0403

Gnomad4 NFE AF: 0.0442

Gnomad4 OTH AF: 0.0846

Alfa AF: 0.0639 Hom.: 217

Bravo AF: 0.107

Asia WGS AF: 0.0980 AC: 340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.91
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs6693036; hg19: chr1-17919817;