15-40458933-C-G

Variant names:

• chr15-40458933-C-G
• rs750392067
• NM_014952.5:c.469C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014952.5(BAHD1):​c.469C>G​(p.Arg157Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,430 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R157C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: BAHD1 NM_014952.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.04
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26966095).

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.469C>G	p.Arg157Gly	missense	Exon 2 of 7	NP_055767.3
	BAHD1	NM_001301132.2		c.469C>G	p.Arg157Gly	missense	Exon 2 of 7	NP_001288061.1	Q8TBE0-2
	BAHD1	NM_001411044.1		c.469C>G	p.Arg157Gly	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.469C>G	p.Arg157Gly	missense	Exon 2 of 7	ENSP00000396976.1	Q8TBE0-1
	BAHD1	ENST00000561234.5	TSL:1	c.469C>G	p.Arg157Gly	missense	Exon 2 of 7	ENSP00000454150.1	Q8TBE0-2
	BAHD1	ENST00000560846.1	TSL:1	c.469C>G	p.Arg157Gly	missense	Exon 1 of 6	ENSP00000454101.1	Q8TBE0-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1442430 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 715454

African (AFR) AF: 0.00 AC: 0 AN: 33048

American (AMR) AF: 0.00 AC: 0 AN: 43040

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24724

East Asian (EAS) AF: 0.00 AC: 0 AN: 39492

South Asian (SAS) AF: 0.00 AC: 0 AN: 83802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51778

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5672

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101418

Other (OTH) AF: 0.0000168 AC: 1 AN: 59456

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.076
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.0
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.16
Sift	Uncertain	0.017	D
Sift4G	Benign	0.30	T
Polyphen		0.63	P
Vest4		0.48
MutPred		0.25		Loss of stability (P = 0.0495)
MVP		0.72
MPC		0.96
ClinPred		0.25	T
GERP RS		4.7
PromoterAI		0.017	Neutral
Varity_R		0.17
gMVP		0.18
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs750392067; hg19: chr15-40751132;