7-101247300-A-AAAAAAAATATAT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000474120.5(FIS1):​c.14+4594_14+4595insATATATTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00954 in 141,980 control chromosomes in the GnomAD database, including 15 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0095 (15 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00954 (1355/141980) while in subpopulation AFR AF = 0.032 (1211/37842). AF 95% confidence interval is 0.0305. There are 15 homozygotes in GnomAd4. There are 636 alleles in the male GnomAd4 subpopulation. Median coverage is 27. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 15 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+4595insATATATTTTTTT		intron	N/A	ENSP00000442056.1	F5H8A8
	FIS1	ENST00000473527.5	TSL:1	n.15-3162_15-3161insATATATTTTTTT		intron	N/A	ENSP00000444771.1	F5H509
	FIS1	ENST00000435848.1	TSL:5	c.15-3162_15-3161insATATATTTTTTT		intron	N/A	ENSP00000413500.1	C9JXH1

Frequencies

GnomAD3 genomes AF: 0.00954 AC: 1355 AN: 141968 Hom.: 15 Cov.: 27

Gnomad AFR AF: 0.0320

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00400

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00242

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00336

Gnomad NFE AF: 0.000923

Gnomad OTH AF: 0.00774

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

GnomAD4 genome AF: 0.00954 AC: 1355 AN: 141980 Hom.: 15 Cov.: 27 AF XY: 0.00927 AC XY: 636 AN XY: 68644

African (AFR) AF: 0.0320 AC: 1211 AN: 37842

American (AMR) AF: 0.00399 AC: 56 AN: 14026

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

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

South Asian (SAS) AF: 0.00243 AC: 11 AN: 4526

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

Middle Eastern (MID) AF: 0.00368 AC: 1 AN: 272

European-Non Finnish (NFE) AF: 0.000923 AC: 61 AN: 66076

Other (OTH) AF: 0.00769 AC: 15 AN: 1950

Alfa AF: 0.00199 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;