dbSNP rs854160: HDC:c.32-106A>G (chr15-50263513-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002112.4(HDC):c.32-106A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,116,686 control chromosomes in the GnomAD database, including 185,412 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 0.58 ( 26136 hom., cov: 33)

Exomes 𝑓: 0.57 ( 159276 hom. )

Consequence

HDC
NM_002112.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.55

Publications

7 publications found

Variant links:

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)

HDC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 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.32-106A>G		intron	N/A	NP_002103.2	P19113-1
	HDC	NM_001306146.2		c.32-106A>G		intron	N/A	NP_001293075.1	P19113-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HDC	ENST00000267845.8	TSL:1 MANE Select	c.32-106A>G	intron	N/A	ENSP00000267845.3	P19113-1
HDC	ENST00000543581.5	TSL:1	c.32-106A>G	intron	N/A	ENSP00000440252.1	P19113-2
HDC	ENST00000558679.1	TSL:1	n.374-106A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.583

AC:

88619

AN:

151926

Hom.:

26105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.607

Gnomad AMI

AF:

0.553

Gnomad AMR

AF:

0.562

Gnomad ASJ

AF:

0.631

Gnomad EAS

AF:

0.364

Gnomad SAS

AF:

0.539

Gnomad FIN

AF:

0.545

Gnomad MID

AF:

0.668

Gnomad NFE

AF:

0.597

Gnomad OTH

AF:

0.601

GnomAD4 exome

AF:

0.569

AC:

548628

AN:

964642

Hom.:

159276

AF XY:

0.571

AC XY:

282460

AN XY:

494518

show subpopulations

African (AFR)

AF:

0.612

AC:

14400

AN:

23530

American (AMR)

AF:

0.474

AC:

16810

AN:

35448

Ashkenazi Jewish (ASJ)

AF:

0.634

AC:

14272

AN:

22512

East Asian (EAS)

AF:

0.334

AC:

11317

AN:

33928

South Asian (SAS)

AF:

0.560

AC:

39806

AN:

71116

European-Finnish (FIN)

AF:

0.549

AC:

21617

AN:

39358

Middle Eastern (MID)

AF:

0.631

AC:

2998

AN:

4754

European-Non Finnish (NFE)

AF:

0.583

AC:

402211

AN:

690008

Other (OTH)

AF:

0.573

AC:

25197

AN:

43988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

12440

24880

37321

49761

62201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8840

17680

26520

35360

44200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.583

AC:

88713

AN:

152044

Hom.:

26136

Cov.:

AF XY:

0.579

AC XY:

43055

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.607

AC:

25152

AN:

41424

American (AMR)

AF:

0.562

AC:

8595

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.631

AC:

2186

AN:

3464

East Asian (EAS)

AF:

0.363

AC:

1885

AN:

5186

South Asian (SAS)

AF:

0.540

AC:

2603

AN:

4822

European-Finnish (FIN)

AF:

0.545

AC:

5758

AN:

10560

Middle Eastern (MID)

AF:

0.667

AC:

196

AN:

294

European-Non Finnish (NFE)

AF:

0.597

AC:

40564

AN:

67970

Other (OTH)

AF:

0.602

AC:

1271

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1908

3816

5725

7633

9541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

746

1492

2238

2984

3730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.575

Hom.:

4111

Bravo

AF:

0.582

Asia WGS

AF:

0.453

AC:

1579

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.017

(source)

DANN

Benign

0.78

PhyloP100

-1.5

PromoterAI

0.0044

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over