chr14-58131719-G-C

Variant summary

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

The NM_001001872.4(ARMH4):ā€‹c.1624C>Gā€‹(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 (ā˜…).

Frequency

Genomes: š‘“ 0.0078 ( 10 hom., cov: 33)
Exomes š‘“: 0.0084 ( 97 hom. )

Consequence

ARMH4
NM_001001872.4 missense, splice_region

Scores

16

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]

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
ARMH4NM_001001872.4 linkuse as main transcriptc.1624C>G p.Gln542Glu missense_variant, splice_region_variant 4/8 ENST00000267485.7 NP_001001872.2
ARMH4NM_001320173.3 linkuse as main transcriptc.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
ARMH4ENST00000267485.7 linkuse as main transcriptc.1624C>G p.Gln542Glu missense_variant, splice_region_variant 4/81 NM_001001872.4 ENSP00000267485 P1Q86TY3-1
ARMH4ENST00000334342.5 linkuse as main transcriptn.1789C>G splice_region_variant, non_coding_transcript_exon_variant 4/51
ARMH4ENST00000555101.1 linkuse as main transcriptc.46C>G p.Gln16Glu missense_variant, splice_region_variant 2/22 ENSP00000477692
ARMH4ENST00000557175.5 linkuse as main transcriptn.1149C>G splice_region_variant, non_coding_transcript_exon_variant 3/43

Frequencies

GnomAD3 genomes
AF:
0.00783
AC:
1191
AN:
152194
Hom.:
10
Cov.:
33
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.:
21
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.:
97
Cov.:
31
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.:
10
Cov.:
33
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.:
3
Bravo
AF:
0.00502
TwinsUK
AF:
0.0116
AC:
43
ALSPAC
AF:
0.0104
AC:
40
ESP6500AA
AF:
0.00159
AC:
7
ESP6500EA
AF:
0.00849
AC:
73
ExAC
AF:
0.00779
AC:
946
Asia WGS
AF:
0.000866
AC:
3
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 submitterclinical testingCeGaT Center for Human Genetics TuebingenApr 01, 2023ARMH4: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.063
BayesDel_addAF
Benign
-0.65
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
3.4
DANN
Benign
0.87
DEOGEN2
Benign
0.0012
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.54
T
MetaRNN
Benign
0.0018
T
MetaSVM
Benign
-0.98
T
MutationTaster
Benign
1.0
N
PROVEAN
Benign
-0.33
N
REVEL
Benign
0.032
Sift
Benign
0.35
T
Sift4G
Benign
0.98
T
Polyphen
0.015
B
Vest4
0.30
MVP
0.030
MPC
0.044
ClinPred
0.0024
T
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.

Other links and lift over

dbSNP: rs45570237; hg19: chr14-58598437; API