7-101247300-A-T

Variant names:

• chr7-101247300-A-T
• rs6953617
• ENST00000474120.5:c.14+4595T>A

Variant summary

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

The ENST00000474120.5(FIS1):​c.14+4595T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 141,792 control chromosomes in the GnomAD database, including 15,328 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: 𝑓 0.46 (15328 hom., cov: 22)
• Consequence: FIS1 ENST00000474120.5 intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -1.09

Genes affected

FIS1 (HGNC:21689): (fission, mitochondrial 1) Enables identical protein binding activity. Involved in several processes, including calcium-mediated signaling using intracellular calcium source; cellular calcium ion homeostasis; and mitochondrion organization. Acts upstream of or within mitochondrion morphogenesis. Located in mitochondrion and peroxisome. Is integral component of mitochondrial outer membrane and integral component of peroxisomal membrane. Part of protein-containing complex. Biomarker of Alzheimer's disease. [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=-1.11).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.485 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
FIS1	ENST00000474120.5	c.14+4595T>A		intron_variant	Intron 1 of 3	1		ENSP00000442056.1
FIS1	ENST00000473527.5	n.15-3161T>A		intron_variant	Intron 1 of 4	1		ENSP00000444771.1
FIS1	ENST00000435848.1	c.15-3161T>A		intron_variant	Intron 1 of 3	5		ENSP00000413500.1

Frequencies

GnomAD3 genomes AF: 0.464 AC: 65831 AN: 141778 Hom.: 15333 Cov.: 22

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.464 AC: 65827 AN: 141792 Hom.: 15328 Cov.: 22 AF XY: 0.465 AC XY: 31878 AN XY: 68544

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.502

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.494

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.462

Alfa AF: 0.491 Hom.: 1919

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

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Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.22
DANN	Benign	0.038

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6953617; hg19: chr7-100890581;