rs2288468

Positions:

• chr5-51387821-T-C

Variant summary

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

The NM_002202.3(ISL1):​c.478+72T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,581,796 control chromosomes in the GnomAD database, including 121,430 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.44 (15664 hom., cov: 33)
  • Exomes 𝑓: 0.38 (105766 hom.)
• Consequence: ISL1 NM_002202.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

Genes affected

ISL1 (HGNC:6132): (ISL LIM homeobox 1) This gene encodes a member of the LIM/homeodomain family of transcription factors. The encoded protein binds to the enhancer region of the insulin gene, among others, and may play an important role in regulating insulin gene expression. The encoded protein is central to the development of pancreatic cell lineages and may also be required for motor neuron generation. Mutations in this gene have been associated with maturity-onset diabetes of the young. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ISL1	NM_002202.3	c.478+72T>C		intron_variant		ENST00000230658.12
ISL1	XM_011543380.3	c.286+72T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ISL1	ENST00000230658.12	c.478+72T>C		intron_variant		1	NM_002202.3	P1
ISL1	ENST00000511384.1	c.478+72T>C		intron_variant		5
ISL1	ENST00000505475.3	n.683+72T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66161 AN: 152002 Hom.: 15631 Cov.: 33

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.399

GnomAD4 exome AF: 0.380 AC: 543361 AN: 1429676 Hom.: 105766 AF XY: 0.378 AC XY: 268433 AN XY: 711078

Gnomad4 AFR exome AF: 0.622

Gnomad4 AMR exome AF: 0.372

Gnomad4 ASJ exome AF: 0.308

Gnomad4 EAS exome AF: 0.203

Gnomad4 SAS exome AF: 0.319

Gnomad4 FIN exome AF: 0.381

Gnomad4 NFE exome AF: 0.387

Gnomad4 OTH exome AF: 0.358

GnomAD4 genome AF: 0.435 AC: 66241 AN: 152120 Hom.: 15664 Cov.: 33 AF XY: 0.428 AC XY: 31809 AN XY: 74358

Gnomad4 AFR AF: 0.616

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.395

Alfa AF: 0.388 Hom.: 11393

Bravo AF: 0.442

Asia WGS AF: 0.309 AC: 1077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.6
DANN	Benign	0.41

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: rs2288468; hg19: chr5-50683655; COSMIC: COSV57934493; COSMIC: COSV57934493;