dbSNP rs2288468: ISL1:c.478+72T>C (chr5-51387821-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.15

Publications

11 publications found

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]

ISL1 Gene-Disease associations (from GenCC):

congenital heart disease
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ISL1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_002202.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002202.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ISL1	NM_002202.3	MANE Select	c.478+72T>C		intron	N/A	NP_002193.2	P61371

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ISL1	ENST00000230658.12	TSL:1 MANE Select	c.478+72T>C	intron	N/A	ENSP00000230658.7	P61371
ISL1	ENST00000511384.1	TSL:5	c.478+72T>C	intron	N/A	ENSP00000422676.1	D6RBJ1
ISL1	ENST00000967706.1		c.29-1825T>C	intron	N/A	ENSP00000637765.1

Frequencies

GnomAD3 genomes

AF:

0.435

AC:

66161

AN:

152002

Hom.:

15631

Cov.:

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

African (AFR)

AF:

0.622

AC:

20415

AN:

32816

American (AMR)

AF:

0.372

AC:

15723

AN:

42252

Ashkenazi Jewish (ASJ)

AF:

0.308

AC:

7932

AN:

25716

East Asian (EAS)

AF:

0.203

AC:

7823

AN:

38602

South Asian (SAS)

AF:

0.319

AC:

26826

AN:

84176

European-Finnish (FIN)

AF:

0.381

AC:

18482

AN:

48478

Middle Eastern (MID)

AF:

0.342

AC:

1821

AN:

5322

European-Non Finnish (NFE)

AF:

0.387

AC:

423134

AN:

1093112

Other (OTH)

AF:

0.358

AC:

21205

AN:

59202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

18484

36968

55453

73937

92421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13212

26424

39636

52848

66060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.435

AC:

66241

AN:

152120

Hom.:

15664

Cov.:

AF XY:

0.428

AC XY:

31809

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.616

AC:

25547

AN:

41492

American (AMR)

AF:

0.374

AC:

5715

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.291

AC:

1009

AN:

3468

East Asian (EAS)

AF:

0.176

AC:

909

AN:

5154

South Asian (SAS)

AF:

0.311

AC:

1499

AN:

4818

European-Finnish (FIN)

AF:

0.379

AC:

4006

AN:

10580

Middle Eastern (MID)

AF:

0.316

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.386

AC:

26264

AN:

67996

Other (OTH)

AF:

0.395

AC:

836

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1884

3767

5651

7534

9418

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

604

1208

1812

2416

3020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.397

Hom.:

15749

Bravo

AF:

0.442

Asia WGS

AF:

0.309

AC:

1077

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.6

(source)

DANN

Benign

0.41

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over