7-101247300-A-AAAAAAAAATATAT

Variant names:

• chr7-101247300-A-AAAAAAAAATATAT
• rs762133451
• ENST00000474120.5:c.14+4594_14+4595insATATATTTTTTTT

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The ENST00000474120.5(FIS1):​c.14+4594_14+4595insATATATTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 141,914 control chromosomes in the GnomAD database, including 16 homozygotes. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: 𝑓 0.012 (16 hom., cov: 27)
• Consequence: FIS1 ENST00000474120.5 intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -2.26

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 Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0122 (1736/141914) while in subpopulation NFE AF= 0.0205 (1354/65956). AF 95% confidence interval is 0.0196. There are 16 homozygotes in gnomad4. There are 786 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 16 AR gene

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+4594_14+4595insATATATTTTTTTT		intron_variant	Intron 1 of 3	1		ENSP00000442056.1
FIS1	ENST00000473527.5	n.15-3162_15-3161insATATATTTTTTTT		intron_variant	Intron 1 of 4	1		ENSP00000444771.1
FIS1	ENST00000435848.1	c.15-3162_15-3161insATATATTTTTTTT		intron_variant	Intron 1 of 3	5		ENSP00000413500.1

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1736 AN: 141900 Hom.: 16 Cov.: 27

Gnomad AFR AF: 0.00349

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00721

Gnomad ASJ AF: 0.0114

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.00489

Gnomad MID AF: 0.0137

Gnomad NFE AF: 0.0205

Gnomad OTH AF: 0.00878

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

GnomAD4 genome AF: 0.0122 AC: 1736 AN: 141914 Hom.: 16 Cov.: 27 AF XY: 0.0115 AC XY: 786 AN XY: 68610

Gnomad4 AFR AF: 0.00348

Gnomad4 AMR AF: 0.00720

Gnomad4 ASJ AF: 0.0114

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0111

Gnomad4 FIN AF: 0.00489

Gnomad4 NFE AF: 0.0205

Gnomad4 OTH AF: 0.00873

Alfa AF: 0.00455 Hom.: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

-

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs762133451; hg19: chr7-100890581;