ENST00000785372.1:n.827+1825A>G

Variant names:

• chr1-237003918-A-G
• rs4659762
• ENST00000785372.1:n.827+1825A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000785372.1(ENSG00000302268):​n.827+1825A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 152,092 control chromosomes in the GnomAD database, including 22,720 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 0.49 (22720 hom., cov: 33)
• Consequence: ENSG00000302268 ENST00000785372.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230
• Publications: 2 publications found

Genes affected

ENSG00000302268 (HGNC:):

MT1HL1 (HGNC:31864): (metallothionein 1H like 1) This gene is a retrotransposed gene, compared to MT1H (GeneID:4496). This retrogene is transcribed. It retains a full-length CDS, and is assumed to be translated. Compared to the MT1H product, this protein product differs at three internal amino acids, two of which are at metal-binding sites. [provided by RefSeq, Mar 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000785372.1. 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
	MT1HL1	NM_001276687.2	MANE Select	c.*269T>C		downstream_gene	N/A	NP_001263616.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000302268	ENST00000785372.1		n.827+1825A>G		intron	N/A
	ENSG00000302268	ENST00000785373.1		n.891-256A>G		intron	N/A
	ENSG00000302268	ENST00000785374.1		n.873-402A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75085 AN: 151974 Hom.: 22719 Cov.: 33

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.494 AC: 75075 AN: 152092 Hom.: 22720 Cov.: 33 AF XY: 0.496 AC XY: 36856 AN XY: 74348

African (AFR) AF: 0.124 AC: 5165 AN: 41510

American (AMR) AF: 0.526 AC: 8041 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2210 AN: 3468

East Asian (EAS) AF: 0.541 AC: 2791 AN: 5158

South Asian (SAS) AF: 0.554 AC: 2671 AN: 4824

European-Finnish (FIN) AF: 0.682 AC: 7204 AN: 10560

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.663 AC: 45061 AN: 67974

Other (OTH) AF: 0.529 AC: 1117 AN: 2112

Alfa AF: 0.599 Hom.: 97930

Bravo AF: 0.469

Asia WGS AF: 0.489 AC: 1705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.48
PhyloP100		0.023
Mutation Taster		=93/7	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4659762; hg19: chr1-237167218;