rs3792733

chr5-51386231-G-Achr5-51386231-G-T

Variant summary

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

The NM_002202.3(ISL1):c.219-1259G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 159,532 control chromosomes in the GnomAD database, including 4,718 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 0.24 (4497 hom., cov: 32)
  • Exomes 𝑓: 0.21 (221 hom.)
• Consequence: ISL1 NM_002202.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0740

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ISL1	NM_002202.3	c.219-1259G>A		intron_variant		ENST00000230658.12
ISL1	XM_011543380.3	c.-370G>A		5_prime_UTR_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ISL1	ENST00000230658.12	c.219-1259G>A		intron_variant		1	NM_002202.3	P1
ISL1	ENST00000511384.1	c.219-1259G>A		intron_variant		5
ISL1	ENST00000505475.3	n.28G>A		non_coding_transcript_exon_variant	1/5	5

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36334 AN: 151984 Hom.: 4486 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.210 AC: 1564 AN: 7430 Hom.: 221 Cov.: 0 AF XY: 0.197 AC XY: 792 AN XY: 4026

Gnomad4 AFR exome AF: 0.210

Gnomad4 AMR exome AF: 0.247

Gnomad4 ASJ exome AF: 0.117

Gnomad4 EAS exome AF: 0.126

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.158

Gnomad4 NFE exome AF: 0.228

Gnomad4 OTH exome AF: 0.179

GnomAD4 genome AF: 0.239 AC: 36385 AN: 152102 Hom.: 4497 Cov.: 32 AF XY: 0.234 AC XY: 17401 AN XY: 74370

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.207

Alfa AF: 0.211 Hom.: 1304

Bravo AF: 0.245

Asia WGS AF: 0.172 AC: 600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	8.0
Dann	Benign	0.73

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: rs3792733; hg19: chr5-50682065;