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GeneBe

rs1549521

chr15-50242635-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_002112.4(HDC):c.1614T>C(p.Asn538=) 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 (★).

Frequency

Genomes: 𝑓 0.12 ( 2790 hom., cov: 32)
Exomes 𝑓: 0.036 ( 3138 hom. )

Consequence

HDC
NM_002112.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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 criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.08 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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/exons MANE UniProt
HDCNM_002112.4 linkuse as main transcriptc.1614T>C p.Asn538= synonymous_variant 12/12 ENST00000267845.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HDCENST00000267845.8 linkuse as main transcriptc.1614T>C p.Asn538= synonymous_variant 12/121 NM_002112.4 P1P19113-1
HDCENST00000543581.5 linkuse as main transcriptc.1515T>C p.Asn505= synonymous_variant 11/111 P19113-2
HDCENST00000559816.1 linkuse as main transcriptn.1358T>C non_coding_transcript_exon_variant 5/52

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.120
AC:
18239
AN:
151988
Hom.:
2775
Cov.:
32
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.:
33
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.120
AC:
18290
AN:
152106
Hom.:
2790
Cov.:
32
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: criteria provided, single submitter
LINK: link

Submissions by phenotype

HDC-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 28, 2019This 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.

Other links and lift over

dbSNP: rs1549521; hg19: chr15-50534832; COSMIC: COSV51068323; COSMIC: COSV51068323; API