15-50262814-C-T

Variant names:

• chr15-50262814-C-T
• rs860526
• NM_002112.4:c.204+421G>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.204+421G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,892 control chromosomes in the GnomAD database, including 21,698 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 0.53 (21698 hom., cov: 30)
• Consequence: HDC NM_002112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.761
• Publications: 10 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: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.566 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDC	NM_002112.4	MANE Select	c.204+421G>A		intron	N/A	NP_002103.2
	HDC	NM_001306146.2		c.204+421G>A		intron	N/A	NP_001293075.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDC	ENST00000267845.8	TSL:1 MANE Select	c.204+421G>A		intron	N/A	ENSP00000267845.3
	HDC	ENST00000543581.5	TSL:1	c.204+421G>A		intron	N/A	ENSP00000440252.1
	HDC	ENST00000558679.1	TSL:1	n.546+421G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80325 AN: 151774 Hom.: 21668 Cov.: 30

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.529 AC: 80425 AN: 151892 Hom.: 21698 Cov.: 30 AF XY: 0.526 AC XY: 39071 AN XY: 74212

African (AFR) AF: 0.500 AC: 20688 AN: 41392

American (AMR) AF: 0.528 AC: 8063 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2065 AN: 3458

East Asian (EAS) AF: 0.182 AC: 935 AN: 5146

South Asian (SAS) AF: 0.511 AC: 2457 AN: 4810

European-Finnish (FIN) AF: 0.532 AC: 5605 AN: 10544

Middle Eastern (MID) AF: 0.613 AC: 179 AN: 292

European-Non Finnish (NFE) AF: 0.571 AC: 38806 AN: 67964

Other (OTH) AF: 0.550 AC: 1159 AN: 2106

Alfa AF: 0.551 Hom.: 103524

Bravo AF: 0.523

Asia WGS AF: 0.355 AC: 1239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.18
DANN	Benign	0.45
PhyloP100		-0.76
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: rs860526; hg19: chr15-50555011;