chr16-56658306-C-T

Variant names:

• chr16-56658306-C-T
• rs2291956
• NM_005949.4:c.28+220C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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]

ENSG00000310278 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005949.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT1F	NM_005949.4	MANE Select	c.28+220C>T		intron	N/A	NP_005940.1
	MT1F	NM_001301272.2		c.28+220C>T		intron	N/A	NP_001288201.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT1F	ENST00000334350.7	TSL:1 MANE Select	c.28+220C>T		intron	N/A	ENSP00000334872.6
	MT1F	ENST00000858841.1		c.28+220C>T		intron	N/A	ENSP00000528900.1
	MT1F	ENST00000568475.1	TSL:2	c.28+220C>T		intron	N/A	ENSP00000456462.1

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

African (AFR) AF: 0.215 AC: 2668 AN: 12414

American (AMR) AF: 0.0671 AC: 1182 AN: 17622

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 1457 AN: 13430

East Asian (EAS) AF: 0.135 AC: 4073 AN: 30118

South Asian (SAS) AF: 0.139 AC: 6173 AN: 44436

European-Finnish (FIN) AF: 0.126 AC: 4422 AN: 35232

Middle Eastern (MID) AF: 0.127 AC: 249 AN: 1966

European-Non Finnish (NFE) AF: 0.122 AC: 33690 AN: 275898

Other (OTH) AF: 0.133 AC: 3423 AN: 25758

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

African (AFR) AF: 0.218 AC: 9069 AN: 41534

American (AMR) AF: 0.0806 AC: 1233 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 360 AN: 3472

East Asian (EAS) AF: 0.160 AC: 828 AN: 5166

South Asian (SAS) AF: 0.144 AC: 695 AN: 4822

European-Finnish (FIN) AF: 0.131 AC: 1388 AN: 10594

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 292

European-Non Finnish (NFE) AF: 0.122 AC: 8271 AN: 68008

Other (OTH) AF: 0.129 AC: 273 AN: 2114

Alfa AF: 0.127 Hom.: 725

Bravo AF: 0.144

Asia WGS AF: 0.174 AC: 603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.74
DANN	Benign	0.68
PhyloP100		-3.2
PromoterAI		0.079	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2291956; hg19: chr16-56692218;