rs374321595

Variant names:

• chr15-40459005-C-G
• rs374321595
• NM_014952.5:c.541C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-40459005-C-G
• chr15-40459005-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014952.5(BAHD1):​c.541C>G​(p.Arg181Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,435,490 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: BAHD1 NM_014952.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06622881).

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.541C>G	p.Arg181Gly	missense	Exon 2 of 7	NP_055767.3
	BAHD1	NM_001301132.2		c.541C>G	p.Arg181Gly	missense	Exon 2 of 7	NP_001288061.1	Q8TBE0-2
	BAHD1	NM_001411044.1		c.541C>G	p.Arg181Gly	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.541C>G	p.Arg181Gly	missense	Exon 2 of 7	ENSP00000396976.1	Q8TBE0-1
	BAHD1	ENST00000561234.5	TSL:1	c.541C>G	p.Arg181Gly	missense	Exon 2 of 7	ENSP00000454150.1	Q8TBE0-2
	BAHD1	ENST00000560846.1	TSL:1	c.541C>G	p.Arg181Gly	missense	Exon 1 of 6	ENSP00000454101.1	Q8TBE0-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1435490 Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1 AN XY: 711174

African (AFR) AF: 0.00 AC: 0 AN: 32844

American (AMR) AF: 0.00 AC: 0 AN: 42270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24434

East Asian (EAS) AF: 0.00 AC: 0 AN: 39378

South Asian (SAS) AF: 0.00 AC: 0 AN: 83242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5624

European-Non Finnish (NFE) AF: 9.11e-7 AC: 1 AN: 1097254

Other (OTH) AF: 0.00 AC: 0 AN: 59064

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.089	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.21
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.12
Sift	Uncertain	0.028	D
Sift4G	Benign	0.072	T
Polyphen		0.0030	B
Vest4		0.23
MutPred		0.26		Gain of glycosylation at S180 (P = 0.0359)
MVP		0.49
MPC		0.33
ClinPred		0.26	T
GERP RS		3.0
Varity_R		0.079
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

Other links and lift over

dbSNP: rs374321595; hg19: chr15-40751204;