rs2241136

Positions:

• chr12-95993294-G-A
• chr12-95993294-G-C

Variant summary

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

The NM_002108.4(HAL):​c.589+157C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,178 control chromosomes in the GnomAD database, including 1,289 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 0.12 (1289 hom., cov: 32)
• Consequence: HAL NM_002108.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790

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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAL	NM_002108.4	c.589+157C>T		intron_variant		ENST00000261208.8	NP_002099.1
HAL	NM_001258334.2	c.589+157C>T		intron_variant			NP_001245263.1
HAL	NM_001258333.2	c.-36+157C>T		intron_variant			NP_001245262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAL	ENST00000261208.8	c.589+157C>T		intron_variant		1	NM_002108.4	ENSP00000261208.3

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17823 AN: 152060 Hom.: 1286 Cov.: 32

Gnomad AFR AF: 0.0980

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.0724

Gnomad ASJ AF: 0.0749

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.117 AC: 17854 AN: 152178 Hom.: 1289 Cov.: 32 AF XY: 0.123 AC XY: 9156 AN XY: 74394

Gnomad4 AFR AF: 0.0983

Gnomad4 AMR AF: 0.0724

Gnomad4 ASJ AF: 0.0749

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.112

Alfa AF: 0.107 Hom.: 2037

Bravo AF: 0.105

Asia WGS AF: 0.291 AC: 1011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.1
DANN	Benign	0.78

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: rs2241136; hg19: chr12-96387072;