rs4242549

Variant names:

• chr8-1922790-G-A
• rs4242549
• NM_014629.4:c.2144-174G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-1922790-G-A
• chr8-1922790-G-C
• chr8-1922790-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014629.4(ARHGEF10):​c.2144-174G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,064 control chromosomes in the GnomAD database, including 27,524 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.60 (27524 hom., cov: 33)
• Consequence: ARHGEF10 NM_014629.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.165
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 8-1922790-G-A is Benign according to our data. Variant chr8-1922790-G-A is described in ClinVar as Benign. ClinVar VariationId is 1234308.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.875 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.2144-174G>A		intron	N/A	NP_055444.2	O15013-5
	ARHGEF10	NM_001438091.1		c.2147-174G>A		intron	N/A	NP_001425020.1
	ARHGEF10	NM_001308153.3		c.2144-174G>A		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.2144-174G>A		intron	N/A	ENSP00000340297.3	O15013-5
	ARHGEF10	ENST00000518288.5	TSL:1	c.2216-174G>A		intron	N/A	ENSP00000431012.1	O15013-6
	ARHGEF10	ENST00000520359.5	TSL:1	c.2030-174G>A		intron	N/A	ENSP00000427909.1	O15013-7

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90712 AN: 151944 Hom.: 27511 Cov.: 33

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.897

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.597 AC: 90756 AN: 152064 Hom.: 27524 Cov.: 33 AF XY: 0.607 AC XY: 45108 AN XY: 74364

African (AFR) AF: 0.542 AC: 22445 AN: 41438

American (AMR) AF: 0.656 AC: 10026 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1937 AN: 3470

East Asian (EAS) AF: 0.897 AC: 4634 AN: 5168

South Asian (SAS) AF: 0.720 AC: 3474 AN: 4824

European-Finnish (FIN) AF: 0.662 AC: 7008 AN: 10582

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39271 AN: 67982

Other (OTH) AF: 0.591 AC: 1246 AN: 2110

Alfa AF: 0.592 Hom.: 13792

Bravo AF: 0.595

Asia WGS AF: 0.815 AC: 2832 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.59
PhyloP100		0.17
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4242549;

hg19: chr8-1870956;