15-50249962-C-G

Variant names:

• chr15-50249962-C-G
• rs854150
• NM_002112.4:c.1042-1619G>C

Variant summary

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

The NM_002112.4(HDC):​c.1042-1619G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,022 control chromosomes in the GnomAD database, including 8,221 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 0.32 (8221 hom., cov: 32)
• Consequence: HDC NM_002112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDC	NM_002112.4	c.1042-1619G>C		intron_variant	Intron 9 of 11	ENST00000267845.8	NP_002103.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDC	ENST00000267845.8	c.1042-1619G>C		intron_variant	Intron 9 of 11	1	NM_002112.4	ENSP00000267845.3
HDC	ENST00000543581.5	c.1041+2468G>C		intron_variant	Intron 9 of 10	1		ENSP00000440252.1
HDC	ENST00000559816.1	n.786-1619G>C		intron_variant	Intron 2 of 4	2

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48802 AN: 151904 Hom.: 8220 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.321 AC: 48830 AN: 152022 Hom.: 8221 Cov.: 32 AF XY: 0.325 AC XY: 24157 AN XY: 74288

African (AFR) AF: 0.223 AC: 9266 AN: 41492

American (AMR) AF: 0.329 AC: 5017 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1191 AN: 3468

East Asian (EAS) AF: 0.329 AC: 1704 AN: 5172

South Asian (SAS) AF: 0.277 AC: 1333 AN: 4816

European-Finnish (FIN) AF: 0.436 AC: 4601 AN: 10554

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24595 AN: 67938

Other (OTH) AF: 0.343 AC: 721 AN: 2104

Alfa AF: 0.338 Hom.: 1152

Bravo AF: 0.305

Asia WGS AF: 0.297 AC: 1035 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.67
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

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: rs854150; hg19: chr15-50542159;