1-37820221-G-T

Variant names:

• chr1-37820221-G-T
• rs4653329
• NM_005955.3:c.1767+1900C>A

Variant summary

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

The NM_005955.3(MTF1):​c.1767+1900C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,046 control chromosomes in the GnomAD database, including 4,502 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 0.23 (4502 hom., cov: 32)
• Consequence: MTF1 NM_005955.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.710
• Publications: 10 publications found

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]

MTF1 Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: G2P

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 = 0.279 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005955.3. 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
	MTF1	NM_005955.3	MANE Select	c.1767+1900C>A		intron	N/A	NP_005946.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTF1	ENST00000373036.5	TSL:1 MANE Select	c.1767+1900C>A		intron	N/A	ENSP00000362127.3

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34713 AN: 151928 Hom.: 4493 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.229 AC: 34751 AN: 152046 Hom.: 4502 Cov.: 32 AF XY: 0.230 AC XY: 17074 AN XY: 74326

African (AFR) AF: 0.115 AC: 4786 AN: 41512

American (AMR) AF: 0.270 AC: 4116 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 403 AN: 3472

East Asian (EAS) AF: 0.217 AC: 1118 AN: 5160

South Asian (SAS) AF: 0.204 AC: 983 AN: 4816

European-Finnish (FIN) AF: 0.332 AC: 3510 AN: 10570

Middle Eastern (MID) AF: 0.147 AC: 43 AN: 292

European-Non Finnish (NFE) AF: 0.282 AC: 19162 AN: 67938

Other (OTH) AF: 0.210 AC: 443 AN: 2108

Alfa AF: 0.236 Hom.: 773

Bravo AF: 0.219

Asia WGS AF: 0.204 AC: 710 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	0.33
DANN	Benign	0.37
PhyloP100		-0.71
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: rs4653329; hg19: chr1-38285893;