rs854163

Variant names:

• chr15-50265541-G-A
• rs854163
• NM_002112.4:c.31+52C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-50265541-G-A
• chr15-50265541-G-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.31+52C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,555,824 control chromosomes in the GnomAD database, including 47,962 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 0.23 (4127 hom., cov: 32)
  • Exomes 𝑓: 0.25 (43835 hom.)
• Consequence: HDC NM_002112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.241
• 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: 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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.259 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.31+52C>T		intron	N/A	NP_002103.2	P19113-1
	HDC	NM_001306146.2		c.31+52C>T		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.31+52C>T		intron	N/A	ENSP00000267845.3	P19113-1
	HDC	ENST00000543581.5	TSL:1	c.31+52C>T		intron	N/A	ENSP00000440252.1	P19113-2
	HDC	ENST00000558679.1	TSL:1	n.373+52C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34606 AN: 152014 Hom.: 4120 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.0856

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.228

GnomAD4 exome AF: 0.246 AC: 345911 AN: 1403692 Hom.: 43835 Cov.: 25 AF XY: 0.248 AC XY: 174211 AN XY: 701604

African (AFR) AF: 0.170 AC: 5493 AN: 32318

American (AMR) AF: 0.148 AC: 6586 AN: 44538

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 6973 AN: 25792

East Asian (EAS) AF: 0.0745 AC: 2936 AN: 39410

South Asian (SAS) AF: 0.245 AC: 20847 AN: 84952

European-Finnish (FIN) AF: 0.314 AC: 16746 AN: 53314

Middle Eastern (MID) AF: 0.228 AC: 1288 AN: 5644

European-Non Finnish (NFE) AF: 0.256 AC: 271036 AN: 1059394

Other (OTH) AF: 0.240 AC: 14006 AN: 58330

GnomAD4 genome AF: 0.228 AC: 34641 AN: 152132 Hom.: 4127 Cov.: 32 AF XY: 0.230 AC XY: 17091 AN XY: 74352

African (AFR) AF: 0.175 AC: 7284 AN: 41508

American (AMR) AF: 0.198 AC: 3029 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 897 AN: 3472

East Asian (EAS) AF: 0.0862 AC: 445 AN: 5164

South Asian (SAS) AF: 0.230 AC: 1112 AN: 4828

European-Finnish (FIN) AF: 0.314 AC: 3322 AN: 10568

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17800 AN: 67990

Other (OTH) AF: 0.232 AC: 490 AN: 2114

Alfa AF: 0.221 Hom.: 1348

Bravo AF: 0.211

Asia WGS AF: 0.166 AC: 579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.5
DANN	Benign	0.77
PhyloP100		-0.24
PromoterAI		0.029	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: rs854163; hg19: chr15-50557738; COSMIC: COSV107263198; COSMIC: COSV107263198;