rs6693036

Variant names:

• chr1-17593322-T-C
• rs6693036
• NM_018125.4:c.257+4843T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018125.4. 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
	ARHGEF10L	NM_018125.4	MANE Select	c.257+4843T>C		intron	N/A	NP_060595.3
	ARHGEF10L	NM_001011722.2		c.257+4843T>C		intron	N/A	NP_001011722.2	Q9HCE6-2
	ARHGEF10L	NM_001438939.1		c.257+4843T>C		intron	N/A	NP_001425868.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF10L	ENST00000361221.8	TSL:1 MANE Select	c.257+4843T>C		intron	N/A	ENSP00000355060.3	Q9HCE6-1
	ARHGEF10L	ENST00000375415.5	TSL:1	c.257+4843T>C		intron	N/A	ENSP00000364564.1	Q9HCE6-2
	ARHGEF10L	ENST00000970707.1		c.257+4843T>C		intron	N/A	ENSP00000640766.1

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

African (AFR) AF: 0.218 AC: 9064 AN: 41514

American (AMR) AF: 0.0568 AC: 869 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0476 AC: 165 AN: 3468

East Asian (EAS) AF: 0.172 AC: 888 AN: 5172

South Asian (SAS) AF: 0.0348 AC: 168 AN: 4830

European-Finnish (FIN) AF: 0.0403 AC: 428 AN: 10618

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0442 AC: 3008 AN: 68028

Other (OTH) AF: 0.0846 AC: 179 AN: 2116

Alfa AF: 0.0664 Hom.: 1171

Bravo AF: 0.107

Asia WGS AF: 0.0980 AC: 340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.91
DANN	Benign	0.41
PhyloP100		-0.48
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: rs6693036; hg19: chr1-17919817;