chr1-37835548-G-A

Position:

• chr1-37835548-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.853+123C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 750,142 control chromosomes in the GnomAD database, including 26,079 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 0.21 (4115 hom., cov: 32)
  • Exomes 𝑓: 0.26 (21964 hom.)
• Consequence: MTF1 NM_005955.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.100

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=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTF1	NM_005955.3	c.853+123C>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.853+123C>T		intron_variant		1	NM_005955.3	ENSP00000362127.3

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31496 AN: 151980 Hom.: 4109 Cov.: 32

Gnomad AFR AF: 0.0524

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.197

GnomAD4 exome AF: 0.264 AC: 158147 AN: 598042 Hom.: 21964 AF XY: 0.261 AC XY: 81848 AN XY: 313256

Gnomad4 AFR exome AF: 0.0496

Gnomad4 AMR exome AF: 0.269

Gnomad4 ASJ exome AF: 0.116

Gnomad4 EAS exome AF: 0.222

Gnomad4 SAS exome AF: 0.203

Gnomad4 FIN exome AF: 0.330

Gnomad4 NFE exome AF: 0.286

Gnomad4 OTH exome AF: 0.241

GnomAD4 genome AF: 0.207 AC: 31508 AN: 152100 Hom.: 4115 Cov.: 32 AF XY: 0.209 AC XY: 15558 AN XY: 74348

Gnomad4 AFR AF: 0.0523

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.195

Alfa AF: 0.231 Hom.: 569

Bravo AF: 0.195

Asia WGS AF: 0.189 AC: 658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.76

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: rs28378413; hg19: chr1-38301220;