rs854151

Variant names:

• chr15-50250522-A-G
• rs854151
• NM_002112.4:c.1041+1908T>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.1041+1908T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,014 control chromosomes in the GnomAD database, including 4,578 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 0.24 (4578 hom., cov: 32)
• Consequence: HDC NM_002112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326
• 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: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

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 (EAS) allele frequency at 95% confidence interval = 0.302 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDC	NM_002112.4	MANE Select	c.1041+1908T>C		intron	N/A	NP_002103.2	P19113-1
	HDC	NM_001306146.2		c.1041+1908T>C		intron	N/A	NP_001293075.1	P19113-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDC	ENST00000267845.8	TSL:1 MANE Select	c.1041+1908T>C		intron	N/A	ENSP00000267845.3	P19113-1
	HDC	ENST00000543581.5	TSL:1	c.1041+1908T>C		intron	N/A	ENSP00000440252.1	P19113-2
	HDC	ENST00000860523.1		c.1146+1908T>C		intron	N/A	ENSP00000530582.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36958 AN: 151896 Hom.: 4576 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.243 AC: 36989 AN: 152014 Hom.: 4578 Cov.: 32 AF XY: 0.247 AC XY: 18337 AN XY: 74278

African (AFR) AF: 0.201 AC: 8334 AN: 41476

American (AMR) AF: 0.236 AC: 3604 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 826 AN: 3472

East Asian (EAS) AF: 0.315 AC: 1624 AN: 5162

South Asian (SAS) AF: 0.248 AC: 1195 AN: 4826

European-Finnish (FIN) AF: 0.312 AC: 3293 AN: 10556

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17299 AN: 67934

Other (OTH) AF: 0.256 AC: 540 AN: 2110

Alfa AF: 0.247 Hom.: 8048

Bravo AF: 0.232

Asia WGS AF: 0.271 AC: 945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.31
DANN	Benign	0.61
PhyloP100		-0.33
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: rs854151; hg19: chr15-50542719;