15-50265541-G-A

Position:

• chr15-50265541-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002112.4(HDC):​c.31+52C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,555,824 control chromosomes in the GnomAD database, including 47,962 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (4127 hom., cov: 32)
  • Exomes 𝑓: 0.25 (43835 hom.)
• Consequence: HDC NM_002112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.241

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDC	NM_002112.4	c.31+52C>T		intron_variant		ENST00000267845.8	NP_002103.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDC	ENST00000267845.8	c.31+52C>T		intron_variant		1	NM_002112.4	ENSP00000267845.3
HDC	ENST00000543581.5	c.31+52C>T		intron_variant		1		ENSP00000440252.1
HDC	ENST00000558679.1	n.373+52C>T		intron_variant		1
HDC	ENST00000558761.5	n.134+52C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34606 AN: 152014 Hom.: 4120 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.0856

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.228

GnomAD4 exome AF: 0.246 AC: 345911 AN: 1403692 Hom.: 43835 Cov.: 25 AF XY: 0.248 AC XY: 174211 AN XY: 701604

Gnomad4 AFR exome AF: 0.170

Gnomad4 AMR exome AF: 0.148

Gnomad4 ASJ exome AF: 0.270

Gnomad4 EAS exome AF: 0.0745

Gnomad4 SAS exome AF: 0.245

Gnomad4 FIN exome AF: 0.314

Gnomad4 NFE exome AF: 0.256

Gnomad4 OTH exome AF: 0.240

GnomAD4 genome AF: 0.228 AC: 34641 AN: 152132 Hom.: 4127 Cov.: 32 AF XY: 0.230 AC XY: 17091 AN XY: 74352

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.258

Gnomad4 EAS AF: 0.0862

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.232

Alfa AF: 0.200 Hom.: 691

Bravo AF: 0.211

Asia WGS AF: 0.166 AC: 579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.5
DANN	Benign	0.77

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

Other links and lift over

dbSNP: rs854163; hg19: chr15-50557738;