rs14375

Variant names:

• chr8-1958464-G-T
• rs14375
• NM_014629.4:c.*1201G>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.*1201G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.935 in 152,252 control chromosomes in the GnomAD database, including 66,559 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 0.93 (66556 hom., cov: 32)
  • Exomes 𝑓: 0.88 (3 hom.)
• Consequence: ARHGEF10 NM_014629.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160
• Publications: 11 publications found

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]

ARHGEF10 Gene-Disease associations (from GenCC):

• autosomal dominant slowed nerve conduction velocity

  Inheritance: AD, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
• hereditary peripheral neuropathy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• peripheral neuropathy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

KBTBD11-OT1 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014629.4. 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
	ARHGEF10	NM_014629.4	MANE Select	c.*1201G>T		3_prime_UTR	Exon 29 of 29	NP_055444.2	O15013-5
	ARHGEF10	NM_001438091.1		c.*1201G>T		3_prime_UTR	Exon 29 of 29	NP_001425020.1
	ARHGEF10	NM_001308153.3		c.*1201G>T		3_prime_UTR	Exon 30 of 30	NP_001295082.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF10	ENST00000349830.8	TSL:1 MANE Select	c.*1201G>T		3_prime_UTR	Exon 29 of 29	ENSP00000340297.3	O15013-5
	ARHGEF10	ENST00000518288.5	TSL:1	c.*1201G>T		3_prime_UTR	Exon 30 of 30	ENSP00000431012.1	O15013-6
	ARHGEF10	ENST00000520359.5	TSL:1	c.*1201G>T		3_prime_UTR	Exon 28 of 28	ENSP00000427909.1	O15013-7

Frequencies

GnomAD3 genomes AF: 0.935 AC: 142198 AN: 152126 Hom.: 66496 Cov.: 32

Gnomad AFR AF: 0.916

Gnomad AMI AF: 0.991

Gnomad AMR AF: 0.930

Gnomad ASJ AF: 0.927

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.985

Gnomad FIN AF: 0.968

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.934

Gnomad OTH AF: 0.919

GnomAD4 exome AF: 0.875 AC: 7 AN: 8 Hom.: 3 Cov.: 0 AF XY: 1.00 AC XY: 4 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.935 AC: 142317 AN: 152244 Hom.: 66556 Cov.: 32 AF XY: 0.938 AC XY: 69831 AN XY: 74438

African (AFR) AF: 0.916 AC: 38044 AN: 41518

American (AMR) AF: 0.930 AC: 14231 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.927 AC: 3220 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5174 AN: 5184

South Asian (SAS) AF: 0.985 AC: 4752 AN: 4826

European-Finnish (FIN) AF: 0.968 AC: 10267 AN: 10610

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.934 AC: 63519 AN: 68022

Other (OTH) AF: 0.920 AC: 1942 AN: 2112

Alfa AF: 0.932 Hom.: 124825

Bravo AF: 0.930

Asia WGS AF: 0.985 AC: 3426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.1
DANN	Benign	0.51
PhyloP100		0.016
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: rs14375; hg19: chr8-1906630;