rs991216

Positions:

• chr5-51392699-C-G
• chr5-51392699-C-T

Variant summary

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

The NM_002202.3(ISL1):​c.934-795C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,018 control chromosomes in the GnomAD database, including 13,701 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 0.41 (13701 hom., cov: 32)
• Consequence: ISL1 NM_002202.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122

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=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ISL1	NM_002202.3	c.934-795C>G		intron_variant		ENST00000230658.12	NP_002193.2
ISL1	XM_011543380.3	c.742-795C>G		intron_variant			XP_011541682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ISL1	ENST00000230658.12	c.934-795C>G		intron_variant		1	NM_002202.3	ENSP00000230658	P1
ISL1	ENST00000511384.1	c.865-795C>G		intron_variant		5		ENSP00000422676
ISL1	ENST00000505475.3	n.1139-795C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62769 AN: 151900 Hom.: 13682 Cov.: 32

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.413 AC: 62828 AN: 152018 Hom.: 13701 Cov.: 32 AF XY: 0.406 AC XY: 30190 AN XY: 74288

Gnomad4 AFR AF: 0.539

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.383

Alfa AF: 0.262 Hom.: 619

Bravo AF: 0.417

Asia WGS AF: 0.296 AC: 1031 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.7
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: rs991216; hg19: chr5-50688533;