Variant chr5-51389680-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_002202.3(ISL1):c.513G>A(p.Arg171=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00454 in 1,612,232 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 97 hom. )

Consequence

ISL1
NM_002202.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.316

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 made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 5-51389680-G-A is Benign according to our data. Variant chr5-51389680-G-A is described in ClinVar as [Benign]. Clinvar id is 778187.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.316 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00361 (549/152268) while in subpopulation SAS AF= 0.0292 (141/4830). AF 95% confidence interval is 0.0253. There are 8 homozygotes in gnomad4. There are 291 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 549 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ISL1	NM_002202.3 linkuse as main transcript	c.513G>A	p.Arg171=	synonymous_variant	4/6	ENST00000230658.12
ISL1	XM_011543380.3 linkuse as main transcript	c.321G>A	p.Arg107=	synonymous_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ISL1	ENST00000230658.12 linkuse as main transcript	c.513G>A	p.Arg171=	synonymous_variant	4/6	1	NM_002202.3	P1
ISL1	ENST00000511384.1 linkuse as main transcript	c.513G>A	p.Arg171=	synonymous_variant	4/6	5
ISL1	ENST00000505475.3 linkuse as main transcript	n.718G>A		non_coding_transcript_exon_variant	3/5	5

Frequencies

GnomAD3 genomes

AF:

0.00361

AC:

549

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.0418

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0292

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00275

Gnomad OTH

AF:

0.00764

GnomAD3 exomes

AF:

0.00659

AC:

1633

AN:

247960

Hom.:

AF XY:

0.00774

AC XY:

1043

AN XY:

134668

show subpopulations

Gnomad AFR exome

AF:

0.000441

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.0341

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.0263

Gnomad FIN exome

AF:

0.000850

Gnomad NFE exome

AF:

0.00313

Gnomad OTH exome

AF:

0.00889

GnomAD4 exome

AF:

0.00464

AC:

6769

AN:

1459964

Hom.:

Cov.:

AF XY:

0.00545

AC XY:

3959

AN XY:

726348

show subpopulations

Gnomad4 AFR exome

AF:

0.000748

Gnomad4 AMR exome

AF:

0.00186

Gnomad4 ASJ exome

AF:

0.0353

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0277

Gnomad4 FIN exome

AF:

0.00106

Gnomad4 NFE exome

AF:

0.00245

Gnomad4 OTH exome

AF:

0.00685

GnomAD4 genome

AF:

0.00361

AC:

549

AN:

152268

Hom.:

Cov.:

AF XY:

0.00391

AC XY:

291

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.0418

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0292

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.00275

Gnomad4 OTH

AF:

0.00756

Alfa

AF:

0.00486

Hom.:

Bravo

AF:

0.00291

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.00507

EpiControl

AF:

0.00462

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

-0.49

CADD

Benign

8.9

DANN

Benign

0.93

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