8-1897844-C-T

Variant names:

• chr8-1897844-C-T
• rs4474061
• NM_014629.4:c.1558-589C>T

Variant summary

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

The NM_014629.4(ARHGEF10):​c.1558-589C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0778 in 152,190 control chromosomes in the GnomAD database, including 555 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 0.078 (555 hom., cov: 32)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.451

Genes affected

ARHGEF10 (HGNC:14103): (Rho guanine nucleotide exchange factor 10) This gene encodes a Rho guanine nucleotide exchange factor (GEF). Rho GEFs regulate the activity of small Rho GTPases by stimulating the exchange of guanine diphosphate (GDP) for guanine triphosphate (GTP) and may play a role in neural morphogenesis. Mutations in this gene are associated with slowed nerve conduction velocity (SNCV). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

KBTBD11-OT1 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF10	NM_014629.4	c.1558-589C>T		intron_variant	Intron 14 of 28	ENST00000349830.8	NP_055444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.1558-589C>T		intron_variant	Intron 14 of 28	1	NM_014629.4	ENSP00000340297.3
KBTBD11-OT1	ENST00000635855.1	n.*1512-589C>T		intron_variant	Intron 15 of 29	5		ENSP00000489726.1

Frequencies

GnomAD3 genomes AF: 0.0777 AC: 11819 AN: 152072 Hom.: 553 Cov.: 32

Gnomad AFR AF: 0.0925

Gnomad AMI AF: 0.0419

Gnomad AMR AF: 0.0927

Gnomad ASJ AF: 0.0827

Gnomad EAS AF: 0.0794

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.0766

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0559

Gnomad OTH AF: 0.0892

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

GnomAD4 genome AF: 0.0778 AC: 11835 AN: 152190 Hom.: 555 Cov.: 32 AF XY: 0.0815 AC XY: 6066 AN XY: 74418

African (AFR) AF: 0.0925 AC: 3839 AN: 41514

American (AMR) AF: 0.0927 AC: 1418 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0827 AC: 287 AN: 3472

East Asian (EAS) AF: 0.0798 AC: 413 AN: 5174

South Asian (SAS) AF: 0.209 AC: 1004 AN: 4810

European-Finnish (FIN) AF: 0.0766 AC: 813 AN: 10612

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0559 AC: 3800 AN: 68008

Other (OTH) AF: 0.0920 AC: 194 AN: 2108

Alfa AF: 0.0660 Hom.: 648

Bravo AF: 0.0769

Asia WGS AF: 0.151 AC: 527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.78
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4474061; hg19: chr8-1846010;