15-50256046-C-T

Variant names:

• chr15-50256046-C-T
• rs2853766
• NM_002112.4:c.441+1379G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002112.4(HDC):​c.441+1379G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,142 control chromosomes in the GnomAD database, including 3,068 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (3068 hom., cov: 32)
• Consequence: HDC NM_002112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.328
• Publications: 7 publications found

Genes affected

HDC (HGNC:4855): (histidine decarboxylase) This gene encodes a member of the group II decarboxylase family and forms a homodimer that converts L-histidine to histamine in a pyridoxal phosphate dependent manner. Histamine regulates several physiologic processes, including neurotransmission, gastric acid secretion,inflamation, and smooth muscle tone.[provided by RefSeq, Aug 2010]

HDC Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002112.4. 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
	HDC	NM_002112.4	MANE Select	c.441+1379G>A		intron	N/A	NP_002103.2	P19113-1
	HDC	NM_001306146.2		c.441+1379G>A		intron	N/A	NP_001293075.1	P19113-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDC	ENST00000267845.8	TSL:1 MANE Select	c.441+1379G>A		intron	N/A	ENSP00000267845.3	P19113-1
	HDC	ENST00000543581.5	TSL:1	c.441+1379G>A		intron	N/A	ENSP00000440252.1	P19113-2
	HDC	ENST00000558679.1	TSL:1	n.783+1379G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27692 AN: 152026 Hom.: 3068 Cov.: 32

Gnomad AFR AF: 0.0474

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.202

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.182 AC: 27702 AN: 152142 Hom.: 3068 Cov.: 32 AF XY: 0.187 AC XY: 13901 AN XY: 74368

African (AFR) AF: 0.0473 AC: 1966 AN: 41538

American (AMR) AF: 0.210 AC: 3211 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 775 AN: 3468

East Asian (EAS) AF: 0.313 AC: 1618 AN: 5176

South Asian (SAS) AF: 0.235 AC: 1132 AN: 4818

European-Finnish (FIN) AF: 0.268 AC: 2821 AN: 10540

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.228 AC: 15496 AN: 68002

Other (OTH) AF: 0.204 AC: 430 AN: 2108

Alfa AF: 0.210 Hom.: 11899

Bravo AF: 0.169

Asia WGS AF: 0.236 AC: 822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.64
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

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: rs2853766; hg19: chr15-50548243;