15-40458921-C-T

Variant names:

• chr15-40458921-C-T
• rs369397772
• NM_014952.5:c.457C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

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. 14/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.865
• Publications: 0 publications found

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]

ENSG00000302612 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014952.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAHD1	NM_014952.5	MANE Select	c.457C>T	p.Arg153Cys	missense	Exon 2 of 7	NP_055767.3
	BAHD1	NM_001301132.2		c.457C>T	p.Arg153Cys	missense	Exon 2 of 7	NP_001288061.1	Q8TBE0-2
	BAHD1	NM_001411044.1		c.457C>T	p.Arg153Cys	missense	Exon 2 of 7	NP_001397973.1	Q8TBE0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BAHD1	ENST00000416165.6	TSL:1 MANE Select	c.457C>T	p.Arg153Cys	missense	Exon 2 of 7	ENSP00000396976.1	Q8TBE0-1
	BAHD1	ENST00000561234.5	TSL:1	c.457C>T	p.Arg153Cys	missense	Exon 2 of 7	ENSP00000454150.1	Q8TBE0-2
	BAHD1	ENST00000560846.1	TSL:1	c.457C>T	p.Arg153Cys	missense	Exon 1 of 6	ENSP00000454101.1	Q8TBE0-3

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152208 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.0000640 AC: 15 AN: 234258 AF XY: 0.0000471

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 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

African (AFR) AF: 0.0000302 AC: 1 AN: 33100

American (AMR) AF: 0.000231 AC: 10 AN: 43292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24892

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39520

South Asian (SAS) AF: 0.000119 AC: 10 AN: 84108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51792

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5670

European-Non Finnish (NFE) AF: 0.0000109 AC: 12 AN: 1102658

Other (OTH) AF: 0.0000336 AC: 2 AN: 59552

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152208 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74346

African (AFR) AF: 0.000121 AC: 5 AN: 41456

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

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

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.86
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.22	N
REVEL	Benign	0.23
Sift	Benign	0.12	T
Sift4G	Benign	0.086	T
Polyphen		0.0030	B
Vest4		0.40
MVP		0.91
MPC		0.60
ClinPred		0.076	T
GERP RS		3.5
PromoterAI		-0.021	Neutral
Varity_R		0.071
gMVP		0.24
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs369397772; hg19: chr15-40751120; COSMIC: COSV107520473; COSMIC: COSV107520473;