rs35047996

Variant names:

• chr15-50266000-T-C
• rs35047996
• ENST00000558679.1:n.-35A>G

Your query was ambiguous. Multiple possible variants found:

• 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 ENST00000558679.1(HDC):​n.-35A>G 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDC	ENST00000558679.1	n.-35A>G		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;