rs1549521

Variant names:

• chr15-50242635-A-G
• rs1549521
• NM_002112.4:c.1614T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_002112.4(HDC):​c.1614T>C​(p.Asn538Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0438 in 1,613,986 control chromosomes in the GnomAD database, including 5,928 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.12 (2790 hom., cov: 32)
  • Exomes 𝑓: 0.036 (3138 hom.)
• Consequence: HDC NM_002112.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.07
• Publications: 9 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 15-50242635-A-G is Benign according to our data. Variant chr15-50242635-A-G is described in ClinVar as Benign. ClinVar VariationId is 3060900.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.08 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.352 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.1614T>C	p.Asn538Asn	synonymous	Exon 12 of 12	NP_002103.2	P19113-1
	HDC	NM_001306146.2		c.1515T>C	p.Asn505Asn	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.1614T>C	p.Asn538Asn	synonymous	Exon 12 of 12	ENSP00000267845.3	P19113-1
	HDC	ENST00000543581.5	TSL:1	c.1515T>C	p.Asn505Asn	synonymous	Exon 11 of 11	ENSP00000440252.1	P19113-2
	HDC	ENST00000860523.1		c.1719T>C	p.Asn573Asn	synonymous	Exon 12 of 12	ENSP00000530582.1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18239 AN: 151988 Hom.: 2775 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0462

Gnomad ASJ AF: 0.0234

Gnomad EAS AF: 0.0923

Gnomad SAS AF: 0.00851

Gnomad FIN AF: 0.00849

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0279

Gnomad OTH AF: 0.0771

GnomAD2 exomes AF: 0.0498 AC: 12523 AN: 251430 AF XY: 0.0423

Gnomad AFR exome AF: 0.362

Gnomad AMR exome AF: 0.0236

Gnomad ASJ exome AF: 0.0257

Gnomad EAS exome AF: 0.0924

Gnomad FIN exome AF: 0.00836

Gnomad NFE exome AF: 0.0280

Gnomad OTH exome AF: 0.0329

GnomAD4 exome AF: 0.0358 AC: 52360 AN: 1461880 Hom.: 3138 Cov.: 33 AF XY: 0.0339 AC XY: 24660 AN XY: 727242

African (AFR) AF: 0.378 AC: 12646 AN: 33478

American (AMR) AF: 0.0270 AC: 1208 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 648 AN: 26136

East Asian (EAS) AF: 0.0672 AC: 2666 AN: 39700

South Asian (SAS) AF: 0.0112 AC: 966 AN: 86258

European-Finnish (FIN) AF: 0.00979 AC: 523 AN: 53418

Middle Eastern (MID) AF: 0.0269 AC: 155 AN: 5768

European-Non Finnish (NFE) AF: 0.0274 AC: 30506 AN: 1112002

Other (OTH) AF: 0.0504 AC: 3042 AN: 60396

GnomAD4 genome AF: 0.120 AC: 18290 AN: 152106 Hom.: 2790 Cov.: 32 AF XY: 0.114 AC XY: 8513 AN XY: 74354

African (AFR) AF: 0.357 AC: 14803 AN: 41458

American (AMR) AF: 0.0462 AC: 706 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0234 AC: 81 AN: 3464

East Asian (EAS) AF: 0.0909 AC: 471 AN: 5180

South Asian (SAS) AF: 0.00831 AC: 40 AN: 4816

European-Finnish (FIN) AF: 0.00849 AC: 90 AN: 10596

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0279 AC: 1898 AN: 68000

Other (OTH) AF: 0.0763 AC: 161 AN: 2110

Alfa AF: 0.0604 Hom.: 1504

Bravo AF: 0.136

Asia WGS AF: 0.0690 AC: 241 AN: 3478

EpiCase AF: 0.0291

EpiControl AF: 0.0275

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	HDC-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.051
DANN	Benign	0.49
PhyloP100		-1.1
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: rs1549521; hg19: chr15-50534832; COSMIC: COSV51068323; COSMIC: COSV51068323;