15-50242506-C-T

Variant names:

• chr15-50242506-C-T
• rs16963485
• NM_002112.4:c.1743G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002112.4(HDC):​c.1743G>A​(p.Thr581Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00358 in 1,614,144 control chromosomes in the GnomAD database, including 147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0074 (32 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (115 hom.)
• Consequence: HDC NM_002112.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.45
• 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: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 15-50242506-C-T is Benign according to our data. Variant chr15-50242506-C-T is described in ClinVar as Benign. ClinVar VariationId is 773049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.45 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0841 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.1743G>A	p.Thr581Thr	synonymous	Exon 12 of 12	NP_002103.2	P19113-1
	HDC	NM_001306146.2		c.1644G>A	p.Thr548Thr	synonymous	Exon 11 of 11	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.1743G>A	p.Thr581Thr	synonymous	Exon 12 of 12	ENSP00000267845.3	P19113-1
	HDC	ENST00000543581.5	TSL:1	c.1644G>A	p.Thr548Thr	synonymous	Exon 11 of 11	ENSP00000440252.1	P19113-2
	HDC	ENST00000860523.1		c.1848G>A	p.Thr616Thr	synonymous	Exon 12 of 12	ENSP00000530582.1

Frequencies

GnomAD3 genomes AF: 0.00744 AC: 1132 AN: 152140 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.0922

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.00719

GnomAD2 exomes AF: 0.00849 AC: 2135 AN: 251474 AF XY: 0.00748

Gnomad AFR exome AF: 0.0143

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.00179

Gnomad EAS exome AF: 0.0922

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000730

Gnomad OTH exome AF: 0.00440

GnomAD4 exome AF: 0.00318 AC: 4656 AN: 1461886 Hom.: 115 Cov.: 33 AF XY: 0.00311 AC XY: 2264 AN XY: 727244

African (AFR) AF: 0.0139 AC: 464 AN: 33480

American (AMR) AF: 0.00112 AC: 50 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00157 AC: 41 AN: 26136

East Asian (EAS) AF: 0.0670 AC: 2658 AN: 39700

South Asian (SAS) AF: 0.00159 AC: 137 AN: 86258

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53420

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.000829 AC: 922 AN: 1112004

Other (OTH) AF: 0.00616 AC: 372 AN: 60396

GnomAD4 genome AF: 0.00739 AC: 1125 AN: 152258 Hom.: 32 Cov.: 32 AF XY: 0.00743 AC XY: 553 AN XY: 74450

African (AFR) AF: 0.0130 AC: 542 AN: 41566

American (AMR) AF: 0.00222 AC: 34 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.0908 AC: 470 AN: 5174

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000720 AC: 49 AN: 68014

Other (OTH) AF: 0.00712 AC: 15 AN: 2108

Alfa AF: 0.00208 Hom.: 2

Bravo AF: 0.00832

Asia WGS AF: 0.0410 AC: 144 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.00113

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.11
DANN	Benign	0.68
PhyloP100		-1.4
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: rs16963485; hg19: chr15-50534703; COSMIC: COSV51068318; COSMIC: COSV51068318;