15-40459005-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.541C>T​(p.Arg181Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000768 in 1,587,696 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R181Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000080 ( 0 hom. )

Consequence

BAHD1
NM_014952.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.211
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=0.1238763).
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.541C>T p.Arg181Trp 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.541C>T p.Arg181Trp missense_variant Exon 2 of 7 1 NM_014952.5 ENSP00000396976.1 Q8TBE0-1
BAHD1ENST00000561234.5 linkc.541C>T p.Arg181Trp missense_variant Exon 2 of 7 1 ENSP00000454150.1 Q8TBE0-2
BAHD1ENST00000560846.1 linkc.541C>T p.Arg181Trp missense_variant Exon 1 of 6 1 ENSP00000454101.1 Q8TBE0-3

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152206
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000132
AC:
3
AN:
226702
Hom.:
0
AF XY:
0.0000162
AC XY:
2
AN XY:
123472
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000368
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000197
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000801
AC:
115
AN:
1435490
Hom.:
0
Cov.:
30
AF XY:
0.0000759
AC XY:
54
AN XY:
711174
show subpopulations
Gnomad4 AFR exome
AF:
0.0000304
Gnomad4 AMR exome
AF:
0.0000237
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000240
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000966
Gnomad4 OTH exome
AF:
0.0000847
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152206
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000305
Hom.:
0
Bravo
AF:
0.0000491
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 25, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.541C>T (p.R181W) 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 541, causing the arginine (R) at amino acid position 181 to be replaced by a tryptophan (W). 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
0.11
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.42
.;T;.
Eigen
Benign
-0.057
Eigen_PC
Benign
-0.083
FATHMM_MKL
Benign
0.093
N
LIST_S2
Benign
0.78
T;T;T
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.12
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.34
N;N;N
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-2.1
N;N;N
REVEL
Benign
0.15
Sift
Benign
0.038
D;D;D
Sift4G
Uncertain
0.012
D;D;D
Polyphen
0.99
D;D;D
Vest4
0.18
MVP
0.31
MPC
0.24
ClinPred
0.74
D
GERP RS
3.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.055
gMVP
0.19

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: rs374321595; hg19: chr15-40751204; COSMIC: COSV69084923; COSMIC: COSV69084923; API