8-1909127-A-G

Position:

• chr8-1909127-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000349830.8(ARHGEF10):​c.1968-168A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 152,092 control chromosomes in the GnomAD database, including 25,707 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.58 (25707 hom., cov: 33)
• Consequence: ARHGEF10 ENST00000349830.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.44

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 8-1909127-A-G is Benign according to our data. Variant chr8-1909127-A-G is described in ClinVar as [Benign]. Clinvar id is 1262906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF10	NM_014629.4	c.1968-168A>G		intron_variant		ENST00000349830.8	NP_055444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF10	ENST00000349830.8	c.1968-168A>G		intron_variant		1	NM_014629.4	ENSP00000340297	P4

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87691 AN: 151974 Hom.: 25684 Cov.: 33

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.577 AC: 87771 AN: 152092 Hom.: 25707 Cov.: 33 AF XY: 0.582 AC XY: 43242 AN XY: 74340

Gnomad4 AFR AF: 0.648

Gnomad4 AMR AF: 0.551

Gnomad4 ASJ AF: 0.540

Gnomad4 EAS AF: 0.582

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.538

Gnomad4 OTH AF: 0.558

Alfa AF: 0.534 Hom.: 33756

Bravo AF: 0.571

Asia WGS AF: 0.551 AC: 1917 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.085
DANN	Benign	0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2294035; hg19: chr8-1857293;