5-51387821-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.15
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
ISL1NM_002202.3 linkuse as main transcriptc.478+72T>C intron_variant ENST00000230658.12
ISL1XM_011543380.3 linkuse as main transcriptc.286+72T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ISL1ENST00000230658.12 linkuse as main transcriptc.478+72T>C intron_variant 1 NM_002202.3 P1
ISL1ENST00000511384.1 linkuse as main transcriptc.478+72T>C intron_variant 5
ISL1ENST00000505475.3 linkuse as main transcriptn.683+72T>C intron_variant, non_coding_transcript_variant 5

Frequencies

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

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