Genetic Variant NM_003709.4:c.734-101A>G (chr2-207088682-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003709.4(KLF7):c.734-101A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,296,648 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

KLF7
NM_003709.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.151

Publications

5 publications found

Variant links:

Genes affected

KLF7 (HGNC:6350): (KLF transcription factor 7) The protein encoded by this gene is a member of the Kruppel-like transcriptional regulator family. Members in this family regulate cell proliferation, differentiation and survival and contain three C2H2 zinc fingers at the C-terminus that mediate binding to GC-rich sites. This protein may contribute to the progression of type 2 diabetes by inhibiting insulin expression and secretion in pancreatic beta-cells and by deregulating adipocytokine secretion in adipocytes. A pseudogene of this gene is located on the long arm of chromosome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

KLF7 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P

KLF7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BS2

High AC in GnomAd4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003709.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KLF7	NM_003709.4	MANE Select	c.734-101A>G	intron	N/A	NP_003700.1
KLF7	NM_001270944.2		c.650-101A>G	intron	N/A	NP_001257873.1
KLF7	NM_001270943.2		c.635-101A>G	intron	N/A	NP_001257872.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KLF7	ENST00000309446.11	TSL:1 MANE Select	c.734-101A>G	intron	N/A	ENSP00000309570.6
KLF7	ENST00000421199.5	TSL:1	c.635-101A>G	intron	N/A	ENSP00000387510.1
KLF7	ENST00000423015.5	TSL:1	c.532-101A>G	intron	N/A	ENSP00000398572.1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000149

AC:

AN:

1144394

Hom.:

AF XY:

0.0000160

AC XY:

AN XY:

563616

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26614

American (AMR)

AF:

0.000322

AC:

AN:

27984

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18004

East Asian (EAS)

AF:

0.00

AC:

AN:

36954

South Asian (SAS)

AF:

0.00

AC:

AN:

55244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34736

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4808

European-Non Finnish (NFE)

AF:

0.00000448

AC:

AN:

892176

Other (OTH)

AF:

0.0000836

AC:

AN:

47874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74444

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41568

American (AMR)

AF:

0.000523

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2112

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00233887), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

9.3

(source)

DANN

Benign

0.82

PhyloP100

-0.15

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over