dbSNP rs3792733: ISL1:c.219-1259G>A (chr5-51386231-G-A) – 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.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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0740

Publications

2 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 links:

Genome browser will be placed here

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=-0.8).

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 rank	MANE	Protein	UniProt
ISL1	NM_002202.3 link	c.219-1259G>A		intron_variant	Intron 2 of 5	ENST00000230658.12	NP_002193.2
ISL1	XM_011543380.3 link	c.-370G>A		5_prime_UTR_variant	Exon 1 of 5		XP_011541682.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
ISL1	ENST00000230658.12 link	c.219-1259G>A	intron_variant	Intron 2 of 5	1	NM_002202.3	ENSP00000230658.7
ISL1	ENST00000505475.3 link	n.28G>A	non_coding_transcript_exon_variant	Exon 1 of 5	5
ISL1	ENST00000511384.1 link	c.219-1259G>A	intron_variant	Intron 2 of 5	5		ENSP00000422676.1

Frequencies

GnomAD3 genomes

AF:

0.239

AC:

36334

AN:

151984

Hom.:

4486

Cov.:

show subpopulations

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.:

AF XY:

0.197

AC XY:

792

AN XY:

4026

show subpopulations

African (AFR)

AF:

0.210

AC:

AN:

100

American (AMR)

AF:

0.247

AC:

252

AN:

1022

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

AN:

East Asian (EAS)

AF:

0.126

AC:

AN:

198

South Asian (SAS)

AF:

0.127

AC:

112

AN:

882

European-Finnish (FIN)

AF:

0.158

AC:

AN:

158

Middle Eastern (MID)

AF:

0.150

AC:

AN:

European-Non Finnish (NFE)

AF:

0.228

AC:

1055

AN:

4620

Other (OTH)

AF:

0.179

AC:

AN:

336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

116

173

231

289

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.239

AC:

36385

AN:

152102

Hom.:

4497

Cov.:

AF XY:

0.234

AC XY:

17401

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.272

AC:

11270

AN:

41490

American (AMR)

AF:

0.253

AC:

3862

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

501

AN:

3468

East Asian (EAS)

AF:

0.145

AC:

751

AN:

5178

South Asian (SAS)

AF:

0.133

AC:

639

AN:

4814

European-Finnish (FIN)

AF:

0.216

AC:

2284

AN:

10582

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.241

AC:

16368

AN:

67978

Other (OTH)

AF:

0.207

AC:

438

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1441

2883

4324

5766

7207

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

384

768

1152

1536

1920

<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:

0.216

Hom.:

1678

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

(source)

DANN

Benign

0.73

PhyloP100

-0.074

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over