NM_002202.3:c.219-1259G>A

Variant names:

• chr5-51386231-G-A
• rs3792733
• NM_002202.3:c.219-1259G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0740
• Publications: 2 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]

ACMG classification

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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ISL1	NM_002202.3	MANE Select	c.219-1259G>A		intron	N/A	NP_002193.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ISL1	ENST00000230658.12	TSL:1 MANE Select	c.219-1259G>A		intron	N/A	ENSP00000230658.7
	ISL1	ENST00000505475.3	TSL:5	n.28G>A		non_coding_transcript_exon	Exon 1 of 5
	ISL1	ENST00000511384.1	TSL:5	c.219-1259G>A		intron	N/A	ENSP00000422676.1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36334 AN: 151984 Hom.: 4486 Cov.: 32

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.: 0 AF XY: 0.197 AC XY: 792 AN XY: 4026

African (AFR) AF: 0.210 AC: 21 AN: 100

American (AMR) AF: 0.247 AC: 252 AN: 1022

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 11 AN: 94

East Asian (EAS) AF: 0.126 AC: 25 AN: 198

South Asian (SAS) AF: 0.127 AC: 112 AN: 882

European-Finnish (FIN) AF: 0.158 AC: 25 AN: 158

Middle Eastern (MID) AF: 0.150 AC: 3 AN: 20

European-Non Finnish (NFE) AF: 0.228 AC: 1055 AN: 4620

Other (OTH) AF: 0.179 AC: 60 AN: 336

GnomAD4 genome AF: 0.239 AC: 36385 AN: 152102 Hom.: 4497 Cov.: 32 AF XY: 0.234 AC XY: 17401 AN XY: 74370

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: 51 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16368 AN: 67978

Other (OTH) AF: 0.207 AC: 438 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.0
DANN	Benign	0.73
PhyloP100		-0.074
Mutation Taster		=100/0	polymorphism (auto)

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: rs3792733; hg19: chr5-50682065;