chr5-51394261-A-T

Position:

• chr5-51394261-A-T

Variant summary

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

The NM_002202.3(ISL1):​c.*651A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,534 control chromosomes in the GnomAD database, including 15,658 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 0.43 (15622 hom., cov: 31)
  • Exomes 𝑓: 0.37 (36 hom.)
• Consequence: ISL1 NM_002202.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.609

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=-0.6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ISL1	NM_002202.3	c.*651A>T		3_prime_UTR_variant	6/6	ENST00000230658.12	NP_002193.2
ISL1	XM_011543380.3	c.*651A>T		3_prime_UTR_variant	5/5		XP_011541682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ISL1	ENST00000230658.12	c.*651A>T		3_prime_UTR_variant	6/6	1	NM_002202.3	ENSP00000230658	P1

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66030 AN: 151862 Hom.: 15589 Cov.: 31

Gnomad AFR AF: 0.614

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: 0.366 AC: 203 AN: 554 Hom.: 36 Cov.: 0 AF XY: 0.383 AC XY: 125 AN XY: 326

Gnomad4 AMR exome AF: 0.357

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.392

Gnomad4 NFE exome AF: 0.274

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.435 AC: 66110 AN: 151980 Hom.: 15622 Cov.: 31 AF XY: 0.428 AC XY: 31754 AN XY: 74270

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.395

Alfa AF: 0.243 Hom.: 523

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	-0.60
CADD	Benign	15
DANN	Benign	0.89

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: rs1017; hg19: chr5-50690095;