rs12667992

Variant names:

• chr7-91715762-G-A
• rs12667992
• ENST00000454222.5:n.160-22303C>T

Variant summary

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

The ENST00000454222.5(MTERF1):​n.160-22303C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,046 control chromosomes in the GnomAD database, including 1,376 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 0.13 (1376 hom., cov: 31)
• Consequence: MTERF1 ENST00000454222.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111
• Publications: 5 publications found

Genes affected

MTERF1 (HGNC:21463): (mitochondrial transcription termination factor 1) This gene encodes a mitochondrial transcription termination factor. This protein participates in attenuating transcription from the mitochondrial genome; this attenuation allows higher levels of expression of 16S ribosomal RNA relative to the tRNA gene downstream. The product of this gene has three leucine zipper motifs bracketed by two basic domains that are all required for DNA binding. There is evidence that, for this protein, the zippers participate in intramolecular interactions that establish the three-dimensional structure required for DNA binding. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTERF1	ENST00000454222.5	n.160-22303C>T		intron_variant	Intron 3 of 4	5

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19557 AN: 151926 Hom.: 1379 Cov.: 31

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.192

Gnomad NFE AF: 0.0972

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.129 AC: 19570 AN: 152046 Hom.: 1376 Cov.: 31 AF XY: 0.132 AC XY: 9823 AN XY: 74324

African (AFR) AF: 0.155 AC: 6431 AN: 41430

American (AMR) AF: 0.120 AC: 1829 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 546 AN: 3470

East Asian (EAS) AF: 0.302 AC: 1559 AN: 5160

South Asian (SAS) AF: 0.204 AC: 984 AN: 4814

European-Finnish (FIN) AF: 0.108 AC: 1146 AN: 10570

Middle Eastern (MID) AF: 0.188 AC: 55 AN: 292

European-Non Finnish (NFE) AF: 0.0972 AC: 6609 AN: 68004

Other (OTH) AF: 0.134 AC: 283 AN: 2110

Alfa AF: 0.112 Hom.: 3338

Bravo AF: 0.131

Asia WGS AF: 0.213 AC: 739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.72
PhyloP100		0.11

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12667992; hg19: chr7-91345077;