rs2241136

Variant names:

• chr12-95993294-G-A
• rs2241136
• NM_002108.4:c.589+157C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAL	NM_002108.4	MANE Select	c.589+157C>T		intron	N/A	NP_002099.1	P42357-1
	HAL	NM_001258334.2		c.589+157C>T		intron	N/A	NP_001245263.1	P42357-2
	HAL	NM_001258333.2		c.-36+157C>T		intron	N/A	NP_001245262.1	P42357-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAL	ENST00000261208.8	TSL:1 MANE Select	c.589+157C>T		intron	N/A	ENSP00000261208.3	P42357-1
	HAL	ENST00000546999.5	TSL:1	n.*18+157C>T		intron	N/A	ENSP00000447675.1	Q4VB95
	HAL	ENST00000865988.1		c.589+157C>T		intron	N/A	ENSP00000536047.1

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

African (AFR) AF: 0.0983 AC: 4085 AN: 41542

American (AMR) AF: 0.0724 AC: 1106 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0749 AC: 260 AN: 3472

East Asian (EAS) AF: 0.332 AC: 1720 AN: 5174

South Asian (SAS) AF: 0.234 AC: 1128 AN: 4826

European-Finnish (FIN) AF: 0.184 AC: 1947 AN: 10568

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7312 AN: 67998

Other (OTH) AF: 0.112 AC: 236 AN: 2112

Alfa AF: 0.107 Hom.: 4004

Bravo AF: 0.105

Asia WGS AF: 0.291 AC: 1011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.1
DANN	Benign	0.78
PhyloP100		0.079
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: rs2241136; hg19: chr12-96387072; COSMIC: COSV107196356; COSMIC: COSV107196356;