Variant chr15-50242506-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002112.4(HDC):c.1743G>A(p.Thr581=) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.45

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDC	NM_002112.4 linkuse as main transcript	c.1743G>A	p.Thr581=	synonymous_variant	12/12	ENST00000267845.8	NP_002103.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDC	ENST00000267845.8 linkuse as main transcript	c.1743G>A	p.Thr581=	synonymous_variant	12/12	1	NM_002112.4	ENSP00000267845	P1	P19113-1
HDC	ENST00000543581.5 linkuse as main transcript	c.1644G>A	p.Thr548=	synonymous_variant	11/11	1		ENSP00000440252		P19113-2
HDC	ENST00000559816.1 linkuse as main transcript	n.1487G>A		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

AF:

0.00744

AC:

1132

AN:

152140

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00849

AC:

2135

AN:

251474

Hom.:

AF XY:

0.00748

AC XY:

1016

AN XY:

135906

show subpopulations

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 SAS exome

AF:

0.00140

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.:

AF XY:

0.00311

AC XY:

2264

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0139

Gnomad4 AMR exome

AF:

0.00112

Gnomad4 ASJ exome

AF:

0.00157

Gnomad4 EAS exome

AF:

0.0670

Gnomad4 SAS exome

AF:

0.00159

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000829

Gnomad4 OTH exome

AF:

0.00616

GnomAD4 genome

AF:

0.00739

AC:

1125

AN:

152258

Hom.:

Cov.:

AF XY:

0.00743

AC XY:

553

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0130

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.0908

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000720

Gnomad4 OTH

AF:

0.00712

Alfa

AF:

0.00190

Hom.:

Bravo

AF:

0.00832

Asia WGS

AF:

0.0410

AC:

144

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.11

DANN

Benign

0.68

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