NM_014629.4:c.38-36_38-33delATCT

Variant names:

• chr8-1857879-GATCT-G
• rs35698984
• NM_014629.4:c.38-36_38-33delATCT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_014629.4(ARHGEF10):​c.38-36_38-33delATCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0921 in 592,244 control chromosomes in the GnomAD database, including 1,996 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.081 (332 hom., cov: 24)
  • Exomes 𝑓: 0.095 (1664 hom.)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.185
• Publications: 1 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: Unknown, AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, 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 -10 ACMG points.

• BP6: Variant 8-1857879-GATCT-G is Benign according to our data. Variant chr8-1857879-GATCT-G is described in ClinVar as Benign. ClinVar VariationId is 1296031.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0988 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.38-36_38-33delATCT		intron	N/A	NP_055444.2	O15013-5
	ARHGEF10	NM_001438091.1		c.38-36_38-33delATCT		intron	N/A	NP_001425020.1
	ARHGEF10	NM_001308153.3		c.38-36_38-33delATCT		intron	N/A	NP_001295082.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF10	ENST00000349830.8	TSL:1 MANE Select	c.38-80_38-77delATCT		intron	N/A	ENSP00000340297.3	O15013-5
	ARHGEF10	ENST00000518288.5	TSL:1	c.110-80_110-77delATCT		intron	N/A	ENSP00000431012.1	O15013-6
	ARHGEF10	ENST00000520359.5	TSL:1	c.38-80_38-77delATCT		intron	N/A	ENSP00000427909.1	O15013-7

Frequencies

GnomAD3 genomes AF: 0.0807 AC: 9153 AN: 113478 Hom.: 332 Cov.: 24

Gnomad AFR AF: 0.0428

Gnomad AMI AF: 0.0106

Gnomad AMR AF: 0.0662

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0516

Gnomad SAS AF: 0.0824

Gnomad FIN AF: 0.0932

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.100

GnomAD4 exome AF: 0.0948 AC: 45382 AN: 478694 Hom.: 1664 AF XY: 0.0961 AC XY: 24410 AN XY: 254030

African (AFR) AF: 0.0409 AC: 464 AN: 11356

American (AMR) AF: 0.0543 AC: 1237 AN: 22790

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 1693 AN: 13718

East Asian (EAS) AF: 0.0306 AC: 844 AN: 27572

South Asian (SAS) AF: 0.0932 AC: 4228 AN: 45372

European-Finnish (FIN) AF: 0.0885 AC: 3012 AN: 34048

Middle Eastern (MID) AF: 0.146 AC: 333 AN: 2278

European-Non Finnish (NFE) AF: 0.105 AC: 31173 AN: 296704

Other (OTH) AF: 0.0965 AC: 2398 AN: 24856

GnomAD4 genome AF: 0.0806 AC: 9155 AN: 113550 Hom.: 332 Cov.: 24 AF XY: 0.0796 AC XY: 4385 AN XY: 55056

African (AFR) AF: 0.0427 AC: 1162 AN: 27198

American (AMR) AF: 0.0661 AC: 747 AN: 11304

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 333 AN: 2692

East Asian (EAS) AF: 0.0517 AC: 223 AN: 4314

South Asian (SAS) AF: 0.0826 AC: 299 AN: 3620

European-Finnish (FIN) AF: 0.0932 AC: 691 AN: 7416

Middle Eastern (MID) AF: 0.119 AC: 25 AN: 210

European-Non Finnish (NFE) AF: 0.101 AC: 5513 AN: 54574

Other (OTH) AF: 0.0994 AC: 155 AN: 1560

Alfa AF: 0.0325 Hom.: 20

Bravo AF: 0.0593

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.18
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: rs35698984; hg19: chr8-1806045;