chr12-95982007-G-A

Variant names:

• chr12-95982007-G-A
• rs17676451
• NM_002108.4:c.1288-1144C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

HAL Gene-Disease associations (from GenCC):

• histidinemia

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002108.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAL	NM_002108.4	MANE Select	c.1288-1144C>T		intron	N/A	NP_002099.1
	HAL	NM_001258334.2		c.1288-1144C>T		intron	N/A	NP_001245263.1
	HAL	NM_001258333.2		c.664-1144C>T		intron	N/A	NP_001245262.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAL	ENST00000261208.8	TSL:1 MANE Select	c.1288-1144C>T		intron	N/A	ENSP00000261208.3
	HAL	ENST00000546999.5	TSL:1	n.*717-1144C>T		intron	N/A	ENSP00000447675.1
	HAL	ENST00000538703.5	TSL:2	c.1288-1144C>T		intron	N/A	ENSP00000440861.1

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

African (AFR) AF: 0.0418 AC: 1736 AN: 41524

American (AMR) AF: 0.118 AC: 1802 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 580 AN: 3466

East Asian (EAS) AF: 0.0532 AC: 276 AN: 5186

South Asian (SAS) AF: 0.109 AC: 528 AN: 4828

European-Finnish (FIN) AF: 0.140 AC: 1481 AN: 10588

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14929 AN: 67998

Other (OTH) AF: 0.142 AC: 301 AN: 2116

Alfa AF: 0.171 Hom.: 301

Bravo AF: 0.138

Asia WGS AF: 0.0750 AC: 262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.48
PhyloP100		0.029
Mutation Taster		=100/0	polymorphism (auto)

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: rs17676451; hg19: chr12-96375785;