rs991216

Variant names:

• chr5-51392699-C-G
• rs991216
• NM_002202.3:c.934-795C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-51392699-C-G
• chr5-51392699-C-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.934-795C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,018 control chromosomes in the GnomAD database, including 13,701 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 0.41 (13701 hom., cov: 32)
• Consequence: ISL1 NM_002202.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.122
• 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=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 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.934-795C>G		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.934-795C>G		intron	N/A	ENSP00000230658.7	P61371
	ISL1	ENST00000511384.1	TSL:5	c.865-795C>G		intron	N/A	ENSP00000422676.1	D6RBJ1
	ISL1	ENST00000967706.1		c.484-795C>G		intron	N/A	ENSP00000637765.1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62769 AN: 151900 Hom.: 13682 Cov.: 32

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.413 AC: 62828 AN: 152018 Hom.: 13701 Cov.: 32 AF XY: 0.406 AC XY: 30190 AN XY: 74288

African (AFR) AF: 0.539 AC: 22312 AN: 41430

American (AMR) AF: 0.369 AC: 5646 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 997 AN: 3468

East Asian (EAS) AF: 0.176 AC: 908 AN: 5166

South Asian (SAS) AF: 0.312 AC: 1503 AN: 4818

European-Finnish (FIN) AF: 0.378 AC: 3984 AN: 10552

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.386 AC: 26212 AN: 67978

Other (OTH) AF: 0.383 AC: 809 AN: 2110

Alfa AF: 0.262 Hom.: 619

Bravo AF: 0.417

Asia WGS AF: 0.296 AC: 1031 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	2.7
DANN	Benign	0.73
PhyloP100		-0.12
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: rs991216; hg19: chr5-50688533;