rs974508

Variant names:

• chr7-91818703-C-T
• rs974508
• ENST00000454222.5:n.159+8712G>A

Variant summary

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

The ENST00000454222.5(MTERF1):​n.159+8712G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,074 control chromosomes in the GnomAD database, including 2,935 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 0.17 (2935 hom., cov: 32)
• Consequence: MTERF1 ENST00000454222.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 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.159+8712G>A		intron_variant	Intron 3 of 4	5

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25462 AN: 151954 Hom.: 2919 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0886

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0952

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.168 AC: 25516 AN: 152074 Hom.: 2935 Cov.: 32 AF XY: 0.167 AC XY: 12430 AN XY: 74344

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.0886

Gnomad4 NFE AF: 0.0952

Gnomad4 OTH AF: 0.153

Alfa AF: 0.112 Hom.: 602

Bravo AF: 0.177

Asia WGS AF: 0.218 AC: 756 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	7.0
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs974508; hg19: chr7-91448017;