rs571342427

Variant names:

• chr11-2161289-T-C
• rs571342427

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP6

The variant allele was found at a frequency of 0.000814 in 328,176 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00075 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00087 (1 hom.)
• Consequence: Unknown
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:3
• Conservation: PhyloP100: -4.11

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 11-2161289-T-C is Benign according to our data. Variant chr11-2161289-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 435509.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=3}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.000750 AC: 114 AN: 151988 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00124

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.000869 AC: 153 AN: 176070 Hom.: 1 Cov.: 0 AF XY: 0.000951 AC XY: 85 AN XY: 89392

Gnomad4 AFR exome AF: 0.000155

Gnomad4 AMR exome AF: 0.000680

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000519

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00122

Gnomad4 OTH exome AF: 0.000824

GnomAD4 genome AF: 0.000749 AC: 114 AN: 152106 Hom.: 1 Cov.: 33 AF XY: 0.000605 AC XY: 45 AN XY: 74376

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.000785

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00124

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000555 Hom.: 0

Bravo AF: 0.000854

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2 Benign:3

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Benign:2

Dec 09, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

INS: BP5, BS1 -

not specified Uncertain:1

Feb 02, 2017

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

INS-related disorder Uncertain:1

Jul 09, 2024

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

The INS c.-139A>G variant is located in the 5' untranslated region. This variant was reported in an individual with type 2 diabetes mellitus (reported as c.−80A>G in Malecki et al 2006. PubMed ID: 16741735). This variant is reported in 0.12% of alleles in individuals of Latino descent in gnomAD. This variant has interpretations of likely benign (3) to uncertain significance (1) in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/435509/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Type 2 diabetes mellitus Benign:1

-

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: research

Potent mutations in the INS gene can cause early onset diabetes mellitus which is insulin dependent. May have poor response to sulfonylureas, mutations in this gene can cause beta cell destruction.Though rs571342427 is prevalent in Type Il Diabetes Mellitus cases, more evidence is required to ascertain the significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.2
DANN	Benign	0.88

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs571342427; hg19: chr11-2182519;