Variant chr5-51389734-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_002202.3(ISL1):c.567C>T(p.Asn189=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0064 in 1,614,118 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0044 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0066 ( 47 hom. )

Consequence

ISL1
NM_002202.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0490

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 5-51389734-C-T is Benign according to our data. Variant chr5-51389734-C-T is described in ClinVar as [Benign]. Clinvar id is 778320.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.049 with no splicing effect.

BS2

High AC in GnomAd4 at 663 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ISL1	NM_002202.3 linkuse as main transcript	c.567C>T	p.Asn189=	synonymous_variant	4/6	ENST00000230658.12
ISL1	XM_011543380.3 linkuse as main transcript	c.375C>T	p.Asn125=	synonymous_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ISL1	ENST00000230658.12 linkuse as main transcript	c.567C>T	p.Asn189=	synonymous_variant	4/6	1	NM_002202.3	P1
ISL1	ENST00000511384.1 linkuse as main transcript	c.567C>T	p.Asn189=	synonymous_variant	4/6	5
ISL1	ENST00000505475.3 linkuse as main transcript	n.772C>T		non_coding_transcript_exon_variant	3/5	5

Frequencies

GnomAD3 genomes

AF:

0.00437

AC:

665

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00688

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00570

AC:

1430

AN:

251096

Hom.:

AF XY:

0.00622

AC XY:

844

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00359

Gnomad ASJ exome

AF:

0.00199

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0111

Gnomad FIN exome

AF:

0.00208

Gnomad NFE exome

AF:

0.00753

Gnomad OTH exome

AF:

0.00473

GnomAD4 exome

AF:

0.00662

AC:

9672

AN:

1461838

Hom.:

Cov.:

AF XY:

0.00677

AC XY:

4924

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.00131

Gnomad4 AMR exome

AF:

0.00373

Gnomad4 ASJ exome

AF:

0.00233

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0121

Gnomad4 FIN exome

AF:

0.00234

Gnomad4 NFE exome

AF:

0.00702

Gnomad4 OTH exome

AF:

0.00662

GnomAD4 genome

AF:

0.00435

AC:

663

AN:

152280

Hom.:

Cov.:

AF XY:

0.00414

AC XY:

308

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0116

Gnomad4 FIN

AF:

0.00207

Gnomad4 NFE

AF:

0.00688

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00515

Hom.:

Bravo

AF:

0.00414

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.00769

EpiControl

AF:

0.00806

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

6.9

DANN

Benign

0.94

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over