Variant chr15-50242769-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002112.4(HDC):c.1480A>G(p.Ile494Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00586 in 1,613,824 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 24 hom. )

Consequence

HDC
NM_002112.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.576

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002978623).

BP6

Variant 15-50242769-T-C is Benign according to our data. Variant chr15-50242769-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 713554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 584 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDC	NM_002112.4 linkuse as main transcript	c.1480A>G	p.Ile494Val	missense_variant	12/12	ENST00000267845.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDC	ENST00000267845.8 linkuse as main transcript	c.1480A>G	p.Ile494Val	missense_variant	12/12	1	NM_002112.4	P1	P19113-1
HDC	ENST00000543581.5 linkuse as main transcript	c.1381A>G	p.Ile461Val	missense_variant	11/11	1			P19113-2
HDC	ENST00000559816.1 linkuse as main transcript	n.1224A>G		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes

AF:

0.00384

AC:

584

AN:

151924

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00160

Gnomad AMI

AF:

0.0352

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00649

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00350

AC:

878

AN:

250832

Hom.:

AF XY:

0.00375

AC XY:

509

AN XY:

135746

show subpopulations

Gnomad AFR exome

AF:

0.00175

Gnomad AMR exome

AF:

0.00150

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00238

Gnomad FIN exome

AF:

0.000325

Gnomad NFE exome

AF:

0.00612

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00607

AC:

8872

AN:

1461782

Hom.:

Cov.:

AF XY:

0.00608

AC XY:

4422

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.00131

Gnomad4 AMR exome

AF:

0.00163

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00268

Gnomad4 FIN exome

AF:

0.000694

Gnomad4 NFE exome

AF:

0.00740

Gnomad4 OTH exome

AF:

0.00404

GnomAD4 genome

AF:

0.00384

AC:

584

AN:

152042

Hom.:

Cov.:

AF XY:

0.00369

AC XY:

274

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.00159

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00649

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00567

Hom.:

Bravo

AF:

0.00404

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00908

AC:

ESP6500AA

AF:

0.00205

AC:

ESP6500EA

AF:

0.00710

AC:

ExAC

AF:

0.00351

AC:

426

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00682

EpiControl

AF:

0.00610

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2022	HDC: BP4, BS1, BS2 -
Likely 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

Benign

0.072

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.049

DANN

Benign

0.46

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.54

T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.0030

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.090

N;N

REVEL

Benign

0.010

Sift

Benign

0.68

T;T

Sift4G

Benign

0.96

T;T

Polyphen

0.0

B;.

Vest4

0.041

MVP

0.17

MPC

0.23

ClinPred

0.0015

GERP RS

-7.6

Varity_R

0.018

gMVP

0.37

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