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. The variant received -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
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

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

African (AFR) AF: 0.00246 AC: 13 AN: 5278

American (AMR) AF: 0.00491 AC: 40 AN: 8154

Ashkenazi Jewish (ASJ) AF: 0.00531 AC: 21 AN: 3958

East Asian (EAS) AF: 0.00 AC: 0 AN: 8122

South Asian (SAS) AF: 0.00121 AC: 28 AN: 23058

European-Finnish (FIN) AF: 0.0197 AC: 121 AN: 6132

Middle Eastern (MID) AF: 0.00166 AC: 1 AN: 602

European-Non Finnish (NFE) AF: 0.0141 AC: 1290 AN: 91474

Other (OTH) AF: 0.0112 AC: 94 AN: 8384

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

African (AFR) AF: 0.00207 AC: 86 AN: 41526

American (AMR) AF: 0.00969 AC: 148 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00635 AC: 22 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4824

European-Finnish (FIN) AF: 0.0150 AC: 159 AN: 10588

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0129 AC: 877 AN: 68000

Other (OTH) AF: 0.0128 AC: 27 AN: 2114

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
PhyloP100		-1.7
PromoterAI		0.0015	Neutral
Mutation Taster		=300/0	polymorphism

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

Other links and lift over

dbSNP: rs35047996; hg19: chr15-50558197;