rs854158

chr15-50260880-A-Gchr15-50260880-A-T

Variant summary

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

The NM_002112.4(HDC):c.204+2355T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 151,894 control chromosomes in the GnomAD database, including 5,628 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 0.26 (5628 hom., cov: 30)
• Consequence: HDC NM_002112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDC	NM_002112.4	c.204+2355T>C		intron_variant		ENST00000267845.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDC	ENST00000267845.8	c.204+2355T>C		intron_variant		1	NM_002112.4	P1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40112 AN: 151774 Hom.: 5628 Cov.: 30

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.266

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.264 AC: 40145 AN: 151894 Hom.: 5628 Cov.: 30 AF XY: 0.265 AC XY: 19693 AN XY: 74248

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.268

Alfa AF: 0.283 Hom.: 3401

Bravo AF: 0.246

Asia WGS AF: 0.229 AC: 800 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	13
Dann	Benign	0.81

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: rs854158; hg19: chr15-50553077; COSMIC: COSV51068560;