Variant 15-50242592-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002112.4(HDC):c.1657T>C(p.Phe553Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00389 in 1,614,148 control chromosomes in the GnomAD database, including 194 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.021 ( 102 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 92 hom. )

Consequence

HDC
NM_002112.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.74

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043698847).

BP6

Variant 15-50242592-A-G is Benign according to our data. Variant chr15-50242592-A-G is described in ClinVar as [Benign]. Clinvar id is 776888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0709 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.1657T>C	p.Phe553Leu	missense_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.1657T>C	p.Phe553Leu	missense_variant	12/12	1	NM_002112.4	ENSP00000267845	P1	P19113-1
HDC	ENST00000543581.5 linkuse as main transcript	c.1558T>C	p.Phe520Leu	missense_variant	11/11	1		ENSP00000440252		P19113-2
HDC	ENST00000559816.1 linkuse as main transcript	n.1401T>C		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

AF:

0.0206

AC:

3135

AN:

152140

Hom.:

101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0729

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00522

AC:

1312

AN:

251482

Hom.:

AF XY:

0.00391

AC XY:

531

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.0714

Gnomad AMR exome

AF:

0.00321

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000193

Gnomad OTH exome

AF:

0.00195

GnomAD4 exome

AF:

0.00214

AC:

3131

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

1342

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0756

Gnomad4 AMR exome

AF:

0.00324

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000998

Gnomad4 OTH exome

AF:

0.00517

GnomAD4 genome

AF:

0.0207

AC:

3153

AN:

152258

Hom.:

102

Cov.:

AF XY:

0.0198

AC XY:

1475

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0731

Gnomad4 AMR

AF:

0.00471

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00379

Hom.:

Bravo

AF:

0.0233

ESP6500AA

AF:

0.0726

AC:

319

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00669

AC:

812

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000296

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

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

T;.

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.82

T;T

MetaRNN

Benign

0.0044

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.1

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.16

Sift

Uncertain

0.0080

D;D

Sift4G

Benign

0.64

T;T

Polyphen

0.98

D;.

Vest4

0.60

MutPred

0.22

Gain of helix (P = 0.0325);.;

MVP

0.42

MPC

0.75

ClinPred

0.022

GERP RS

5.7

Varity_R

0.19

gMVP

0.32

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