rs8029889

Variant names:

• chr15-50258703-C-T
• rs8029889
• NM_002112.4:c.205-186G>A

Variant summary

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

The NM_002112.4(HDC):​c.205-186G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,168 control chromosomes in the GnomAD database, including 2,443 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 0.17 (2443 hom., cov: 32)
• Consequence: HDC NM_002112.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HDC	NM_002112.4	c.205-186G>A		intron_variant	Intron 2 of 11	ENST00000267845.8	NP_002103.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HDC	ENST00000267845.8	c.205-186G>A		intron_variant	Intron 2 of 11	1	NM_002112.4	ENSP00000267845.3

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26151 AN: 152050 Hom.: 2444 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.0728

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.0977

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.172 AC: 26173 AN: 152168 Hom.: 2443 Cov.: 32 AF XY: 0.168 AC XY: 12533 AN XY: 74390

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.0729

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.0977

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.209

Alfa AF: 0.205 Hom.: 4825

Bravo AF: 0.178

Asia WGS AF: 0.149 AC: 520 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	4.6
DANN	Benign	0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs8029889; hg19: chr15-50550900;