2-10054360-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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]

KLF11 Gene-Disease associations (from GenCC):

• maturity-onset diabetes of the young type 7

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• maturity-onset diabetes of the young

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• monogenic diabetes

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000271787 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003597.5. 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
	KLF11	NM_003597.5	MANE Select	c.*1853T>C		3_prime_UTR	Exon 4 of 4	NP_003588.1
	KLF11	NM_001177716.2		c.*1853T>C		3_prime_UTR	Exon 4 of 4	NP_001171187.1
	KLF11	NM_001177718.2		c.*1853T>C		3_prime_UTR	Exon 4 of 4	NP_001171189.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF11	ENST00000305883.6	TSL:1 MANE Select	c.*1853T>C		3_prime_UTR	Exon 4 of 4	ENSP00000307023.1
	KLF11	ENST00000535335.1	TSL:2	c.*1853T>C		3_prime_UTR	Exon 4 of 4	ENSP00000442722.1
	KLF11	ENST00000540845.5	TSL:2	c.*1853T>C		3_prime_UTR	Exon 4 of 4	ENSP00000444690.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.917 AC: 22 AN: 24

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.544 AC: 22581 AN: 41498

American (AMR) AF: 0.627 AC: 9574 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1799 AN: 3468

East Asian (EAS) AF: 0.682 AC: 3537 AN: 5184

South Asian (SAS) AF: 0.544 AC: 2625 AN: 4826

European-Finnish (FIN) AF: 0.682 AC: 7214 AN: 10574

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 35026 AN: 67988

Other (OTH) AF: 0.534 AC: 1130 AN: 2116

Alfa AF: 0.522 Hom.: 93056

Bravo AF: 0.548

Asia WGS AF: 0.590 AC: 2050 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Maturity-onset diabetes of the young type 7 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.1
DANN	Benign	0.79
PhyloP100		-0.59
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: rs7632; hg19: chr2-10194487;