rs2291956

Positions:

• chr16-56658306-C-T

Variant summary

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

The NM_005949.4(MT1F):​c.28+220C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 609,082 control chromosomes in the GnomAD database, including 5,687 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 0.15 (1800 hom., cov: 33)
  • Exomes 𝑓: 0.13 (3887 hom.)
• Consequence: MT1F NM_005949.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.15

Genes affected

MT1F (HGNC:7398): (metallothionein 1F) Predicted to enable zinc ion binding activity. Involved in cellular response to cadmium ion. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MT1F	NM_005949.4	c.28+220C>T		intron_variant		ENST00000334350.7	NP_005940.1
MT1F	NM_001301272.2	c.28+220C>T		intron_variant			NP_001288201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT1F	ENST00000334350.7	c.28+220C>T		intron_variant		1	NM_005949.4	ENSP00000334872	P1
MT1F	ENST00000568475.1	c.28+220C>T		intron_variant		2		ENSP00000456462
MT1F	ENST00000564295.1	n.576C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22356 AN: 152090 Hom.: 1797 Cov.: 33

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.0808

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.125 AC: 57337 AN: 456874 Hom.: 3887 Cov.: 5 AF XY: 0.125 AC XY: 30080 AN XY: 239868

Gnomad4 AFR exome AF: 0.215

Gnomad4 AMR exome AF: 0.0671

Gnomad4 ASJ exome AF: 0.108

Gnomad4 EAS exome AF: 0.135

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.126

Gnomad4 NFE exome AF: 0.122

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome AF: 0.147 AC: 22388 AN: 152208 Hom.: 1800 Cov.: 33 AF XY: 0.147 AC XY: 10924 AN XY: 74400

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.0806

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.129

Alfa AF: 0.127 Hom.: 655

Bravo AF: 0.144

Asia WGS AF: 0.174 AC: 603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.74
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2291956; hg19: chr16-56692218;