2-10054360-T-C

Variant names:

• chr2-10054360-T-C
• rs7632
• NM_003597.5:c.*1853T>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003597.5(KLF11):​c.*1853T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 152,166 control chromosomes in the GnomAD database, including 23,432 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (23422 hom., cov: 33)
  • Exomes 𝑓: 0.88 (10 hom.)
• Consequence: KLF11 NM_003597.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.586

Genes affected

KLF11 (HGNC:11811): (KLF transcription factor 11) The protein encoded by this gene is a zinc finger transcription factor that binds to SP1-like sequences in epsilon- and gamma-globin gene promoters. This binding inhibits cell growth and causes apoptosis. Defects in this gene are a cause of maturity-onset diabetes of the young type 7 (MODY7). Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Apr 2010]

ENSG00000271787 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-10054360-T-C is Benign according to our data. Variant chr2-10054360-T-C is described in ClinVar as [Benign]. Clinvar id is 330674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF11	NM_003597.5	c.*1853T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000305883.6	NP_003588.1
KLF11	NM_001177716.2	c.*1853T>C		3_prime_UTR_variant	Exon 4 of 4		NP_001171187.1
KLF11	NM_001177718.2	c.*1853T>C		3_prime_UTR_variant	Exon 4 of 4		NP_001171189.1
KLF11	XM_047446025.1	c.*1853T>C		3_prime_UTR_variant	Exon 4 of 4		XP_047301981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF11	ENST00000305883.6	c.*1853T>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_003597.5	ENSP00000307023.1
KLF11	ENST00000535335.1	c.*1853T>C		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000442722.1
KLF11	ENST00000540845.5	c.*1853T>C		3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000444690.1
ENSG00000271787	ENST00000607181.1	n.*61A>G		downstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83879 AN: 152022 Hom.: 23406 Cov.: 33

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.534

GnomAD4 exome AF: 0.885 AC: 23 AN: 26 Hom.: 10 Cov.: 0 AF XY: 0.900 AC XY: 9 AN XY: 10

Gnomad4 FIN exome AF: 0.917

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.552 AC: 83940 AN: 152140 Hom.: 23422 Cov.: 33 AF XY: 0.561 AC XY: 41698 AN XY: 74366

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.682

Gnomad4 SAS AF: 0.544

Gnomad4 FIN AF: 0.682

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.534

Alfa AF: 0.514 Hom.: 42780

Bravo AF: 0.548

Asia WGS AF: 0.590 AC: 2050 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Maturity-onset diabetes of the young type 7 Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.1
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs7632; hg19: chr2-10194487;