15-40458921-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014952.5(BAHD1):​c.457C>T​(p.Arg153Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000276 in 1,596,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

BAHD1
NM_014952.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.865
Variant links:
Genes affected
BAHD1 (HGNC:29153): (bromo adjacent homology domain containing 1) Enables chromatin binding activity. Involved in heterochromatin assembly and negative regulation of transcription, DNA-templated. Located in nucleoplasm. Part of chromatin silencing complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.08474693).
BS2
High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BAHD1NM_014952.5 linkc.457C>T p.Arg153Cys missense_variant Exon 2 of 7 ENST00000416165.6 NP_055767.3 Q8TBE0-1A0A024R9K2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BAHD1ENST00000416165.6 linkc.457C>T p.Arg153Cys missense_variant Exon 2 of 7 1 NM_014952.5 ENSP00000396976.1 Q8TBE0-1
BAHD1ENST00000561234.5 linkc.457C>T p.Arg153Cys missense_variant Exon 2 of 7 1 ENSP00000454150.1 Q8TBE0-2
BAHD1ENST00000560846.1 linkc.457C>T p.Arg153Cys missense_variant Exon 1 of 6 1 ENSP00000454101.1 Q8TBE0-3

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152208
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000640
AC:
15
AN:
234258
Hom.:
0
AF XY:
0.0000471
AC XY:
6
AN XY:
127378
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000242
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000560
Gnomad SAS exome
AF:
0.000107
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000190
Gnomad OTH exome
AF:
0.000177
GnomAD4 exome
AF:
0.0000256
AC:
37
AN:
1444584
Hom.:
0
Cov.:
30
AF XY:
0.0000377
AC XY:
27
AN XY:
716774
show subpopulations
Gnomad4 AFR exome
AF:
0.0000302
Gnomad4 AMR exome
AF:
0.000231
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.000119
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000109
Gnomad4 OTH exome
AF:
0.0000336
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152208
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264
ESP6500AA
AF:
0.000229
AC:
1
ESP6500EA
AF:
0.000117
AC:
1
ExAC
AF:
0.0000247
AC:
3
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 09, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.457C>T (p.R153C) alteration is located in exon 2 (coding exon 1) of the BAHD1 gene. This alteration results from a C to T substitution at nucleotide position 457, causing the arginine (R) at amino acid position 153 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.094
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.059
.;T;.
Eigen
Benign
-0.75
Eigen_PC
Benign
-0.64
FATHMM_MKL
Benign
0.15
N
LIST_S2
Uncertain
0.87
D;D;D
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.085
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N;N;N
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
0.22
N;N;N
REVEL
Benign
0.23
Sift
Benign
0.12
T;T;T
Sift4G
Benign
0.086
T;T;T
Polyphen
0.0030
B;B;B
Vest4
0.40
MVP
0.91
MPC
0.60
ClinPred
0.076
T
GERP RS
3.5
Varity_R
0.071
gMVP
0.24

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs369397772; hg19: chr15-40751120; API