rs3811911

Variant names:

• chr5-51388617-C-T
• rs3811911
• NM_002202.3:c.478+868C>T

Variant summary

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

The NM_002202.3(ISL1):​c.478+868C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 151,896 control chromosomes in the GnomAD database, including 3,596 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 0.21 (3596 hom., cov: 32)
• Consequence: ISL1 NM_002202.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.451
• Publications: 5 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.239 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ISL1	NM_002202.3	MANE Select	c.478+868C>T		intron	N/A	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.478+868C>T		intron	N/A	ENSP00000230658.7	P61371
	ISL1	ENST00000511384.1	TSL:5	c.478+868C>T		intron	N/A	ENSP00000422676.1	D6RBJ1
	ISL1	ENST00000967706.1		c.29-1029C>T		intron	N/A	ENSP00000637765.1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32308 AN: 151772 Hom.: 3591 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.170

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.191

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.213 AC: 32334 AN: 151896 Hom.: 3596 Cov.: 32 AF XY: 0.208 AC XY: 15474 AN XY: 74218

African (AFR) AF: 0.179 AC: 7419 AN: 41396

American (AMR) AF: 0.246 AC: 3752 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 488 AN: 3466

East Asian (EAS) AF: 0.146 AC: 750 AN: 5152

South Asian (SAS) AF: 0.132 AC: 639 AN: 4828

European-Finnish (FIN) AF: 0.215 AC: 2268 AN: 10558

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16345 AN: 67930

Other (OTH) AF: 0.190 AC: 401 AN: 2108

Alfa AF: 0.229 Hom.: 5242

Bravo AF: 0.215

Asia WGS AF: 0.158 AC: 551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Benign	0.74
PhyloP100		0.45
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: rs3811911; hg19: chr5-50684451;