chr15-50242592-A-G

Variant summary

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

The NM_002112.4(HDC):ā€‹c.1657T>Cā€‹(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 (ā˜…ā˜…). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: š‘“ 0.021 ( 102 hom., cov: 32)
Exomes š‘“: 0.0021 ( 92 hom. )

Consequence

HDC
NM_002112.4 missense

Scores

1
7
10

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]

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 UniProt
HDCNM_002112.4 linkuse as main transcriptc.1657T>C p.Phe553Leu missense_variant 12/12 ENST00000267845.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HDCENST00000267845.8 linkuse as main transcriptc.1657T>C p.Phe553Leu missense_variant 12/121 NM_002112.4 P1P19113-1
HDCENST00000543581.5 linkuse as main transcriptc.1558T>C p.Phe520Leu missense_variant 11/111 P19113-2
HDCENST00000559816.1 linkuse as main transcriptn.1401T>C non_coding_transcript_exon_variant 5/52

Frequencies

GnomAD3 genomes
AF:
0.0206
AC:
3135
AN:
152140
Hom.:
101
Cov.:
32
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.:
40
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.:
92
Cov.:
33
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.:
32
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.:
31
Bravo
AF:
0.0233
ESP6500AA
AF:
0.0726
AC:
319
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00669
AC:
812
Asia WGS
AF:
0.00491
AC:
17
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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.56
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.29
T;.
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.39
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.82
T;T
MetaRNN
Benign
0.0044
T;T
MetaSVM
Benign
-1.2
T
MutationAssessor
Uncertain
2.1
M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.55
T
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
T
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.

Other links and lift over

dbSNP: rs16963486; hg19: chr15-50534789; COSMIC: COSV51074762; COSMIC: COSV51074762; API