chr1-37835804-G-A

Position:

• chr1-37835804-G-A

Variant summary

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

The NM_005955.3(MTF1):​c.780-60C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 1,285,984 control chromosomes in the GnomAD database, including 308,009 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 0.59 (28596 hom., cov: 29)
  • Exomes 𝑓: 0.69 (279413 hom.)
• Consequence: MTF1 NM_005955.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.512

Genes affected

MTF1 (HGNC:7428): (metal regulatory transcription factor 1) This gene encodes a transcription factor that induces expression of metallothioneins and other genes involved in metal homeostasis in response to heavy metals such as cadmium, zinc, copper, and silver. The protein is a nucleocytoplasmic shuttling protein that accumulates in the nucleus upon heavy metal exposure and binds to promoters containing a metal-responsive element (MRE). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTF1	NM_005955.3	c.780-60C>T		intron_variant		ENST00000373036.5	NP_005946.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTF1	ENST00000373036.5	c.780-60C>T		intron_variant		1	NM_005955.3	ENSP00000362127	P1

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90007 AN: 151372 Hom.: 28585 Cov.: 29

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.785

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.613

GnomAD4 exome AF: 0.691 AC: 784271 AN: 1134496 Hom.: 279413 AF XY: 0.689 AC XY: 398213 AN XY: 577666

Gnomad4 AFR exome AF: 0.331

Gnomad4 AMR exome AF: 0.572

Gnomad4 ASJ exome AF: 0.670

Gnomad4 EAS exome AF: 0.549

Gnomad4 SAS exome AF: 0.597

Gnomad4 FIN exome AF: 0.778

Gnomad4 NFE exome AF: 0.722

Gnomad4 OTH exome AF: 0.650

GnomAD4 genome AF: 0.594 AC: 90048 AN: 151488 Hom.: 28596 Cov.: 29 AF XY: 0.596 AC XY: 44108 AN XY: 73984

Gnomad4 AFR AF: 0.360

Gnomad4 AMR AF: 0.592

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.499

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.785

Gnomad4 NFE AF: 0.714

Gnomad4 OTH AF: 0.607

Alfa AF: 0.629 Hom.: 4454

Bravo AF: 0.563

Asia WGS AF: 0.555 AC: 1926 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.3
DANN	Benign	0.49

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: rs3762359; hg19: chr1-38301476;