rs17676451

Positions:

• chr12-95982007-G-A

Variant summary

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

The NM_002108.4(HAL):​c.1288-1144C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,206 control chromosomes in the GnomAD database, including 2,036 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 0.14 (2036 hom., cov: 33)
• Consequence: HAL NM_002108.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290

Genes affected

HAL (HGNC:4806): (histidine ammonia-lyase) Histidine ammonia-lyase is a cytosolic enzyme catalyzing the first reaction in histidine catabolism, the nonoxidative deamination of L-histidine to trans-urocanic acid. Histidine ammonia-lyase defects cause histidinemia which is characterized by increased histidine and histamine and decreased urocanic acid in body fluids. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HAL	NM_002108.4	c.1288-1144C>T		intron_variant		ENST00000261208.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HAL	ENST00000261208.8	c.1288-1144C>T		intron_variant		1	NM_002108.4	P1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21882 AN: 152088 Hom.: 2036 Cov.: 33

Gnomad AFR AF: 0.0419

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.0533

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.144 AC: 21882 AN: 152206 Hom.: 2036 Cov.: 33 AF XY: 0.138 AC XY: 10273 AN XY: 74418

Gnomad4 AFR AF: 0.0418

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.0532

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.142

Alfa AF: 0.175 Hom.: 300

Bravo AF: 0.138

Asia WGS AF: 0.0750 AC: 262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.48

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: rs17676451; hg19: chr12-96375785;