5-51394261-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002202.3(ISL1):​c.*651A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00223 in 152,620 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0022 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0054 (0 hom.)
• 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]

ENSG00000288035 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BS2: High AC in GnomAd4 at 338 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ISL1	NM_002202.3	c.*651A>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000230658.12	NP_002193.2
ISL1	XM_011543380.3	c.*651A>G		3_prime_UTR_variant	Exon 5 of 5		XP_011541682.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ISL1	ENST00000230658.12	c.*651A>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_002202.3	ENSP00000230658.7
ENSG00000288035	ENST00000730931.1	n.*58T>C		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.00222 AC: 338 AN: 151948 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0191

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00179

Gnomad OTH AF: 0.000958

GnomAD4 exome AF: 0.00542 AC: 3 AN: 554 Hom.: 0 Cov.: 0 AF XY: 0.00307 AC XY: 1 AN XY: 326

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 14

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00708 AC: 3 AN: 424

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 106

Other (OTH) AF: 0.00 AC: 0 AN: 8

GnomAD4 genome AF: 0.00222 AC: 338 AN: 152066 Hom.: 0 Cov.: 31 AF XY: 0.00312 AC XY: 232 AN XY: 74330

African (AFR) AF: 0.000217 AC: 9 AN: 41442

American (AMR) AF: 0.000196 AC: 3 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.0191 AC: 202 AN: 10570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00179 AC: 122 AN: 67988

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.00181 Hom.: 523

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	15
DANN	Benign	0.90
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism

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;