dbSNP rs1549521: HDC:p.Asn538Asn (chr15-50242635-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

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

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.07

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDC	NM_002112.4 link	c.1614T>C	p.Asn538Asn	synonymous_variant	Exon 12 of 12	ENST00000267845.8	NP_002103.2	P19113-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HDC	ENST00000267845.8 link	c.1614T>C	p.Asn538Asn	synonymous_variant	Exon 12 of 12	1	NM_002112.4	ENSP00000267845.3	P19113-1
HDC	ENST00000543581.5 link	c.1515T>C	p.Asn505Asn	synonymous_variant	Exon 11 of 11	1		ENSP00000440252.1	P19113-2
HDC	ENST00000559816.1 link	n.1358T>C		non_coding_transcript_exon_variant	Exon 5 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18239

AN:

151988

Hom.:

2775

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0498

AC:

12523

AN:

251430

Hom.:

1270

AF XY:

0.0423

AC XY:

5748

AN XY:

135880

show subpopulations

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 SAS exome

AF:

0.00964

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.:

AF XY:

0.0339

AC XY:

24660

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.378

Gnomad4 AMR exome

AF:

0.0270

Gnomad4 ASJ exome

AF:

0.0248

Gnomad4 EAS exome

AF:

0.0672

Gnomad4 SAS exome

AF:

0.0112

Gnomad4 FIN exome

AF:

0.00979

Gnomad4 NFE exome

AF:

0.0274

Gnomad4 OTH exome

AF:

0.0504

GnomAD4 genome

AF:

0.120

AC:

18290

AN:

152106

Hom.:

2790

Cov.:

AF XY:

0.114

AC XY:

8513

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.357

Gnomad4 AMR

AF:

0.0462

Gnomad4 ASJ

AF:

0.0234

Gnomad4 EAS

AF:

0.0909

Gnomad4 SAS

AF:

0.00831

Gnomad4 FIN

AF:

0.00849

Gnomad4 NFE

AF:

0.0279

Gnomad4 OTH

AF:

0.0763

Alfa

AF:

0.0521

Hom.:

958

Bravo

AF:

0.136

Asia WGS

AF:

0.0690

AC:

241

AN:

3478

EpiCase

AF:

0.0291

EpiControl

AF:

0.0275

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HDC-related disorder

Benign:1

Oct 28, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.051

DANN

Benign

0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over