15-40459042-C-T

Variant names:

• chr15-40459042-C-T
• rs374161184
• NM_014952.5:c.578C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_014952.5(BAHD1):​c.578C>T​(p.Pro193Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,604,986 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (2 hom.)
• Consequence: BAHD1 NM_014952.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.351
• Publications: 1 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03172937).
• BS2: High AC in GnomAd4 at 18 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.578C>T	p.Pro193Leu	missense	Exon 2 of 7	NP_055767.3
	BAHD1	NM_001301132.2		c.578C>T	p.Pro193Leu	missense	Exon 2 of 7	NP_001288061.1	Q8TBE0-2
	BAHD1	NM_001411044.1		c.578C>T	p.Pro193Leu	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.578C>T	p.Pro193Leu	missense	Exon 2 of 7	ENSP00000396976.1	Q8TBE0-1
	BAHD1	ENST00000561234.5	TSL:1	c.578C>T	p.Pro193Leu	missense	Exon 2 of 7	ENSP00000454150.1	Q8TBE0-2
	BAHD1	ENST00000560846.1	TSL:1	c.578C>T	p.Pro193Leu	missense	Exon 1 of 6	ENSP00000454101.1	Q8TBE0-3

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000125 AC: 30 AN: 240466 AF XY: 0.000138

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000179

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000167

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000106 AC: 154 AN: 1452684 Hom.: 2 Cov.: 30 AF XY: 0.000116 AC XY: 84 AN XY: 721642

African (AFR) AF: 0.0000301 AC: 1 AN: 33220

American (AMR) AF: 0.000274 AC: 12 AN: 43828

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25710

East Asian (EAS) AF: 0.00 AC: 0 AN: 39520

South Asian (SAS) AF: 0.000164 AC: 14 AN: 85512

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52444

Middle Eastern (MID) AF: 0.00594 AC: 34 AN: 5728

European-Non Finnish (NFE) AF: 0.0000768 AC: 85 AN: 1106794

Other (OTH) AF: 0.000133 AC: 8 AN: 59928

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152302 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74454

African (AFR) AF: 0.00 AC: 0 AN: 41572

American (AMR) AF: 0.0000653 AC: 1 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68018

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.000115 Hom.: 0

Bravo AF: 0.000140

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000989 AC: 12

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	0.068
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Benign	0.84
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.20	N
PhyloP100		0.35
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.79	N
REVEL	Benign	0.028
Sift	Benign	0.18	T
Sift4G	Benign	0.20	T
Polyphen		0.0	B
Vest4		0.12
MVP		0.11
MPC		0.23
ClinPred		0.0072	T
GERP RS		1.9
Varity_R		0.028
gMVP		0.074
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs374161184; hg19: chr15-40751241;