chr15-50259733-C-T

Variant names:

• chr15-50259733-C-T
• rs1894236
• NM_002112.4:c.205-1216G>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.205-1216G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,086 control chromosomes in the GnomAD database, including 2,427 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 0.17 (2427 hom., cov: 31)
• Consequence: HDC NM_002112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155
• Publications: 6 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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.232 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.205-1216G>A		intron	N/A	NP_002103.2
	HDC	NM_001306146.2		c.205-1216G>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.205-1216G>A		intron	N/A	ENSP00000267845.3
	HDC	ENST00000543581.5	TSL:1	c.205-1216G>A		intron	N/A	ENSP00000440252.1
	HDC	ENST00000558679.1	TSL:1	n.547-1216G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26049 AN: 151968 Hom.: 2428 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.0716

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.0968

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.171 AC: 26071 AN: 152086 Hom.: 2427 Cov.: 31 AF XY: 0.168 AC XY: 12478 AN XY: 74346

African (AFR) AF: 0.119 AC: 4948 AN: 41478

American (AMR) AF: 0.219 AC: 3347 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 802 AN: 3468

East Asian (EAS) AF: 0.0718 AC: 372 AN: 5180

South Asian (SAS) AF: 0.243 AC: 1173 AN: 4826

European-Finnish (FIN) AF: 0.0968 AC: 1024 AN: 10582

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13714 AN: 67974

Other (OTH) AF: 0.210 AC: 443 AN: 2110

Alfa AF: 0.174 Hom.: 1123

Bravo AF: 0.177

Asia WGS AF: 0.149 AC: 521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.7
DANN	Benign	0.77
PhyloP100		0.15
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: rs1894236; hg19: chr15-50551930;