rs3811911

chr5-51388617-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.478+868C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 151,896 control chromosomes in the GnomAD database, including 3,596 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 0.21 (3596 hom., cov: 32)
• Consequence: ISL1 NM_002202.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.451

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=-0.62).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ISL1	NM_002202.3	c.478+868C>T		intron_variant		ENST00000230658.12
ISL1	XM_011543380.3	c.286+868C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ISL1	ENST00000230658.12	c.478+868C>T		intron_variant		1	NM_002202.3	P1
ISL1	ENST00000511384.1	c.478+868C>T		intron_variant		5
ISL1	ENST00000505475.3	n.683+868C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32308 AN: 151772 Hom.: 3591 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.170

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.213 AC: 32334 AN: 151896 Hom.: 3596 Cov.: 32 AF XY: 0.208 AC XY: 15474 AN XY: 74218

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.190

Alfa AF: 0.231 Hom.: 4057

Bravo AF: 0.215

Asia WGS AF: 0.158 AC: 551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	15
Dann	Benign	0.74

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: rs3811911; hg19: chr5-50684451;