rs7182203

Variant names:

• chr15-50260803-G-A
• rs7182203
• NM_002112.4:c.205-2286C>T

Variant summary

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

The NM_002112.4(HDC):​c.205-2286C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,094 control chromosomes in the GnomAD database, including 5,830 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 0.27 (5830 hom., cov: 31)
• Consequence: HDC NM_002112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDC	NM_002112.4	c.205-2286C>T		intron_variant	Intron 2 of 11	ENST00000267845.8	NP_002103.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDC	ENST00000267845.8	c.205-2286C>T		intron_variant	Intron 2 of 11	1	NM_002112.4	ENSP00000267845.3

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40896 AN: 151976 Hom.: 5834 Cov.: 31

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.0971

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.269 AC: 40929 AN: 152094 Hom.: 5830 Cov.: 31 AF XY: 0.265 AC XY: 19704 AN XY: 74358

African (AFR) AF: 0.206 AC: 8561 AN: 41488

American (AMR) AF: 0.315 AC: 4820 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1212 AN: 3468

East Asian (EAS) AF: 0.0975 AC: 505 AN: 5178

South Asian (SAS) AF: 0.278 AC: 1338 AN: 4818

European-Finnish (FIN) AF: 0.221 AC: 2337 AN: 10586

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.311 AC: 21124 AN: 67956

Other (OTH) AF: 0.308 AC: 649 AN: 2110

Alfa AF: 0.307 Hom.: 12107

Bravo AF: 0.272

Asia WGS AF: 0.183 AC: 639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.3
DANN	Benign	0.53
PhyloP100		0.28
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: rs7182203; hg19: chr15-50553000;