Variant 12-95973615-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002108.4(HAL):c.*617G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.029 in 153,054 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 102 hom., cov: 32)

Exomes 𝑓: 0.027 ( 1 hom. )

Consequence

HAL
NM_002108.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.159

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 12-95973615-C-T is Benign according to our data. Variant chr12-95973615-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 310689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.029 (4421/152242) while in subpopulation NFE AF= 0.0433 (2946/68004). AF 95% confidence interval is 0.042. There are 102 homozygotes in gnomad4. There are 2213 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 102 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAL	NM_002108.4 linkuse as main transcript	c.*617G>A		3_prime_UTR_variant	21/21	ENST00000261208.8	NP_002099.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAL	ENST00000261208.8 linkuse as main transcript	c.*617G>A	3_prime_UTR_variant	21/21	1	NM_002108.4	ENSP00000261208	P1	P42357-1
HAL	ENST00000541929.5 linkuse as main transcript	c.*617G>A	3_prime_UTR_variant	20/20	2		ENSP00000446364		P42357-3
HAL	ENST00000544080.6 linkuse as main transcript		downstream_gene_variant		2		ENSP00000439385

Frequencies

GnomAD3 genomes

AF:

0.0291

AC:

4428

AN:

152124

Hom.:

103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00664

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0177

Gnomad ASJ

AF:

0.00979

Gnomad EAS

AF:

0.0148

Gnomad SAS

AF:

0.0350

Gnomad FIN

AF:

0.0548

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0434

Gnomad OTH

AF:

0.0215

GnomAD4 exome

AF:

0.0271

AC:

AN:

812

Hom.:

Cov.:

AF XY:

0.0224

AC XY:

AN XY:

446

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00806

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0517

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0304

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0290

AC:

4421

AN:

152242

Hom.:

102

Cov.:

AF XY:

0.0297

AC XY:

2213

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00662

Gnomad4 AMR

AF:

0.0176

Gnomad4 ASJ

AF:

0.00979

Gnomad4 EAS

AF:

0.0146

Gnomad4 SAS

AF:

0.0346

Gnomad4 FIN

AF:

0.0548

Gnomad4 NFE

AF:

0.0433

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.0381

Hom.:

Bravo

AF:

0.0239

Asia WGS

AF:

0.0320

AC:

111

AN:

3468

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Histidinemia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.55

DANN

Benign

0.27

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over