9-86271915-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030940.4(ISCA1):c.241+92G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 697,280 control chromosomes in the GnomAD database, including 68,972 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (15247 hom., cov: 32)
  • Exomes 𝑓: 0.44 (53725 hom.)
• Consequence: ISCA1 NM_030940.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.641

Genes affected

ISCA1 (HGNC:28660): (iron-sulfur cluster assembly 1) ISCA1 is a mitochondrial protein involved in the biogenesis and assembly of iron-sulfur clusters, which play a role in electron-transfer reactions (Cozar-Castellano et al., 2004 [PubMed 15262227]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 9-86271915-C-T is Benign according to our data. Variant chr9-86271915-C-T is described in ClinVar as [Benign]. Clinvar id is 1262965.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ISCA1	NM_030940.4	c.241+92G>A		intron_variant		ENST00000375991.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ISCA1	ENST00000375991.9	c.241+92G>A		intron_variant		1	NM_030940.4	P1
ISCA1	ENST00000311534.6	c.-54+92G>A		intron_variant		2
ISCA1	ENST00000326094.4	c.241+92G>A		intron_variant		3
ISCA1	ENST00000637705.1	c.178+92G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67602 AN: 151876 Hom.: 15224 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.485

GnomAD4 exome AF: 0.441 AC: 240226 AN: 545288 Hom.: 53725 AF XY: 0.442 AC XY: 129793 AN XY: 293780

Gnomad4 AFR exome AF: 0.460

Gnomad4 AMR exome AF: 0.460

Gnomad4 ASJ exome AF: 0.535

Gnomad4 EAS exome AF: 0.432

Gnomad4 SAS exome AF: 0.470

Gnomad4 FIN exome AF: 0.362

Gnomad4 NFE exome AF: 0.439

Gnomad4 OTH exome AF: 0.459

GnomAD4 genome AF: 0.445 AC: 67671 AN: 151992 Hom.: 15247 Cov.: 32 AF XY: 0.440 AC XY: 32657 AN XY: 74286

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.547

Gnomad4 EAS AF: 0.502

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.492

Alfa AF: 0.435 Hom.: 2265

Bravo AF: 0.456

Asia WGS AF: 0.495 AC: 1720 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	5.2
Dann	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs12351992; hg19: chr9-88886830;