rs1017

Variant names:

• chr5-51394261-A-C
• rs1017
• NM_002202.3:c.*651A>C

Your query was ambiguous. Multiple possible variants found:

• chr5-51394261-A-C
• chr5-51394261-A-G
• chr5-51394261-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002202.3(ISL1):​c.*651A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: ISL1 NM_002202.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.609
• Publications: 28 publications found

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

ENSG00000288035 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).

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.*651A>C		3_prime_UTR	Exon 6 of 6	NP_002193.2	P61371

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ISL1	ENST00000230658.12	TSL:1 MANE Select	c.*651A>C		3_prime_UTR	Exon 6 of 6	ENSP00000230658.7	P61371
	ISL1	ENST00000967706.1		c.*651A>C		3_prime_UTR	Exon 4 of 4	ENSP00000637765.1
	ENSG00000288035	ENST00000730931.1		n.*58T>G		downstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 523

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.88
PhyloP100		0.61

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

Other links and lift over

dbSNP: rs1017; hg19: chr5-50690095;