rs854160

Variant names:

• chr15-50263513-T-C
• rs854160
• NM_002112.4:c.32-106A>G

Variant summary

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

The NM_002112.4(HDC):​c.32-106A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,116,686 control chromosomes in the GnomAD database, including 185,412 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 0.58 (26136 hom., cov: 33)
  • Exomes 𝑓: 0.57 (159276 hom.)
• Consequence: HDC NM_002112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• 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: 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDC	NM_002112.4	c.32-106A>G		intron_variant	Intron 1 of 11	ENST00000267845.8	NP_002103.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDC	ENST00000267845.8	c.32-106A>G		intron_variant	Intron 1 of 11	1	NM_002112.4	ENSP00000267845.3

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88619 AN: 151926 Hom.: 26105 Cov.: 33

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.601

GnomAD4 exome AF: 0.569 AC: 548628 AN: 964642 Hom.: 159276 AF XY: 0.571 AC XY: 282460 AN XY: 494518

African (AFR) AF: 0.612 AC: 14400 AN: 23530

American (AMR) AF: 0.474 AC: 16810 AN: 35448

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 14272 AN: 22512

East Asian (EAS) AF: 0.334 AC: 11317 AN: 33928

South Asian (SAS) AF: 0.560 AC: 39806 AN: 71116

European-Finnish (FIN) AF: 0.549 AC: 21617 AN: 39358

Middle Eastern (MID) AF: 0.631 AC: 2998 AN: 4754

European-Non Finnish (NFE) AF: 0.583 AC: 402211 AN: 690008

Other (OTH) AF: 0.573 AC: 25197 AN: 43988

GnomAD4 genome AF: 0.583 AC: 88713 AN: 152044 Hom.: 26136 Cov.: 33 AF XY: 0.579 AC XY: 43055 AN XY: 74324

African (AFR) AF: 0.607 AC: 25152 AN: 41424

American (AMR) AF: 0.562 AC: 8595 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2186 AN: 3464

East Asian (EAS) AF: 0.363 AC: 1885 AN: 5186

South Asian (SAS) AF: 0.540 AC: 2603 AN: 4822

European-Finnish (FIN) AF: 0.545 AC: 5758 AN: 10560

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.597 AC: 40564 AN: 67970

Other (OTH) AF: 0.602 AC: 1271 AN: 2112

Alfa AF: 0.575 Hom.: 4111

Bravo AF: 0.582

Asia WGS AF: 0.453 AC: 1579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.017
DANN	Benign	0.78
PhyloP100		-1.5
PromoterAI		0.0044	Neutral
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: rs854160; hg19: chr15-50555710; COSMIC: COSV51076659; COSMIC: COSV51076659;