Variant 14-58131719-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001001872.4(ARMH4):c.1624C>G(p.Gln542Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00833 in 1,612,316 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0078 ( 10 hom., cov: 33)

Exomes 𝑓: 0.0084 ( 97 hom. )

Consequence

ARMH4
NM_001001872.4 missense, splice_region

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.396

Variant links:

Genes affected

ARMH4 (HGNC:19846): (armadillo like helical domain containing 4) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARMH4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 14-58131719-G-C is Benign according to our data. Variant chr14-58131719-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2644257.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00839 (12246/1460004) while in subpopulation MID AF= 0.0212 (98/4616). AF 95% confidence interval is 0.0178. There are 97 homozygotes in gnomad4_exome. There are 5922 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMH4	NM_001001872.4 linkuse as main transcript	c.1624C>G	p.Gln542Glu	missense_variant, splice_region_variant	4/8	ENST00000267485.7	NP_001001872.2
ARMH4	NM_001320173.3 linkuse as main transcript	c.1624C>G	p.Gln542Glu	missense_variant, splice_region_variant	4/5		NP_001307102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARMH4	ENST00000267485.7 linkuse as main transcript	c.1624C>G	p.Gln542Glu	missense_variant, splice_region_variant	4/8	1	NM_001001872.4	ENSP00000267485	P1	Q86TY3-1
ARMH4	ENST00000334342.5 linkuse as main transcript	n.1789C>G		splice_region_variant, non_coding_transcript_exon_variant	4/5	1
ARMH4	ENST00000555101.1 linkuse as main transcript	c.46C>G	p.Gln16Glu	missense_variant, splice_region_variant	2/2	2		ENSP00000477692
ARMH4	ENST00000557175.5 linkuse as main transcript	n.1149C>G		splice_region_variant, non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes

AF:

0.00783

AC:

1191

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.0176

Gnomad AMR

AF:

0.00491

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0435

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00807

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00851

AC:

2135

AN:

251026

Hom.:

AF XY:

0.00817

AC XY:

1108

AN XY:

135672

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.00234

Gnomad ASJ exome

AF:

0.00139

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00163

Gnomad FIN exome

AF:

0.0427

Gnomad NFE exome

AF:

0.00866

Gnomad OTH exome

AF:

0.00980

GnomAD4 exome

AF:

0.00839

AC:

12246

AN:

1460004

Hom.:

Cov.:

AF XY:

0.00815

AC XY:

5922

AN XY:

726328

show subpopulations

Gnomad4 AFR exome

AF:

0.00156

Gnomad4 AMR exome

AF:

0.00248

Gnomad4 ASJ exome

AF:

0.00184

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00192

Gnomad4 FIN exome

AF:

0.0406

Gnomad4 NFE exome

AF:

0.00826

Gnomad4 OTH exome

AF:

0.00712

GnomAD4 genome

AF:

0.00782

AC:

1191

AN:

152312

Hom.:

Cov.:

AF XY:

0.00920

AC XY:

685

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00161

Gnomad4 AMR

AF:

0.00490

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0435

Gnomad4 NFE

AF:

0.00807

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00691

Hom.:

Bravo

AF:

0.00502

TwinsUK

AF:

0.0116

AC:

ALSPAC

AF:

0.0104

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00849

AC:

ExAC

AF:

0.00779

AC:

946

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00660

EpiControl

AF:

0.00741

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

ARMH4: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.70

CADD

Benign

3.4

DANN

Benign

0.87

DEOGEN2

Benign

0.0012

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.54

MetaRNN

Benign

0.0018

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

PROVEAN

Benign

-0.33

REVEL

Benign

0.032

Sift

Benign

0.35

Sift4G

Benign

0.98

Polyphen

0.015

Vest4

0.30

MVP

0.030

MPC

0.044

ClinPred

0.0024

GERP RS

-2.4

Varity_R

0.040

gMVP

0.091

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.46

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.46

Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over