rs35047996

Positions:

• chr15-50266000-T-C
• chr15-50266000-T-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The 15-50266000-T-C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00965 in 307,344 control chromosomes in the GnomAD database, including 21 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 0.0089 (7 hom., cov: 32)
  • Exomes 𝑓: 0.010 (14 hom.)
• Consequence: HDC ENST00000558679.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS2: High AC in GnomAd4 at 1357 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDC	ENST00000558679.1			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.00893 AC: 1358 AN: 152064 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00208

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.00977

Gnomad ASJ AF: 0.00635

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0150

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.0129

GnomAD4 exome AF: 0.0104 AC: 1608 AN: 155162 Hom.: 14 Cov.: 0 AF XY: 0.00930 AC XY: 769 AN XY: 82654

Gnomad4 AFR exome AF: 0.00246

Gnomad4 AMR exome AF: 0.00491

Gnomad4 ASJ exome AF: 0.00531

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00121

Gnomad4 FIN exome AF: 0.0197

Gnomad4 NFE exome AF: 0.0141

Gnomad4 OTH exome AF: 0.0112

GnomAD4 genome AF: 0.00892 AC: 1357 AN: 152182 Hom.: 7 Cov.: 32 AF XY: 0.00879 AC XY: 654 AN XY: 74392

Gnomad4 AFR AF: 0.00207

Gnomad4 AMR AF: 0.00969

Gnomad4 ASJ AF: 0.00635

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.0150

Gnomad4 NFE AF: 0.0129

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.0157 Hom.: 5

Bravo AF: 0.00736

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.73
DANN	Benign	0.36

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: rs35047996; hg19: chr15-50558197;