7-101247300-A-AAAAAAATAT

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000474120.5(FIS1):​c.14+4594_14+4595insATATTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00342 in 142,072 control chromosomes in the GnomAD database, including 6 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0034 (6 hom., cov: 27)
• Consequence: FIS1 ENST00000474120.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000474120.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FIS1	ENST00000474120.5	TSL:1	c.14+4594_14+4595insATATTTTTT		intron	N/A	ENSP00000442056.1	F5H8A8
	FIS1	ENST00000473527.5	TSL:1	n.15-3162_15-3161insATATTTTTT		intron	N/A	ENSP00000444771.1	F5H509
	FIS1	ENST00000435848.1	TSL:5	c.15-3162_15-3161insATATTTTTT		intron	N/A	ENSP00000413500.1	C9JXH1

Frequencies

GnomAD3 genomes AF: 0.00342 AC: 486 AN: 142058 Hom.: 6 Cov.: 27

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00243

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000220

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00671

Gnomad NFE AF: 0.0000605

Gnomad OTH AF: 0.000516

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

GnomAD4 genome AF: 0.00342 AC: 486 AN: 142072 Hom.: 6 Cov.: 27 AF XY: 0.00330 AC XY: 227 AN XY: 68686

African (AFR) AF: 0.0117 AC: 444 AN: 37926

American (AMR) AF: 0.00242 AC: 34 AN: 14034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3414

East Asian (EAS) AF: 0.00 AC: 0 AN: 4990

South Asian (SAS) AF: 0.000221 AC: 1 AN: 4526

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7994

Middle Eastern (MID) AF: 0.00735 AC: 2 AN: 272

European-Non Finnish (NFE) AF: 0.0000605 AC: 4 AN: 66076

Other (OTH) AF: 0.000513 AC: 1 AN: 1950

Alfa AF: 0.00 Hom.: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.3

Splicing

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

Other links and lift over

dbSNP: rs762133451; hg19: chr7-100890581;