dbSNP rs7323281: KL:c.820-144A>G (chr13-33053623-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004795.4(KL):c.820-144A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 774,990 control chromosomes in the GnomAD database, including 33,964 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5842 hom., cov: 33)

Exomes 𝑓: 0.30 ( 28122 hom. )

Consequence

KL
NM_004795.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.08

Variant links:

Genes affected

KL (HGNC:6344): (klotho) This gene encodes a type-I membrane protein that is related to beta-glucosidases. Reduced production of this protein has been observed in patients with chronic renal failure (CRF), and this may be one of the factors underlying the degenerative processes (e.g., arteriosclerosis, osteoporosis, and skin atrophy) seen in CRF. Also, mutations within this protein have been associated with ageing and bone loss. [provided by RefSeq, Jul 2008]

KL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 13-33053623-A-G is Benign according to our data. Variant chr13-33053623-A-G is described in ClinVar as [Benign]. Clinvar id is 1233548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
KL	NM_004795.4 link	c.820-144A>G	intron_variant	Intron 1 of 4	ENST00000380099.4	NP_004786.2	Q9UEF7-1
KL	XM_006719895.3 link	c.-102-144A>G	intron_variant	Intron 1 of 4		XP_006719958.1
KL	XM_047430775.1 link	c.820-144A>G	intron_variant	Intron 1 of 3		XP_047286731.1
KL	XM_047430776.1 link	c.820-144A>G	intron_variant	Intron 1 of 3		XP_047286732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KL	ENST00000380099.4 link	c.820-144A>G		intron_variant	Intron 1 of 4	1	NM_004795.4	ENSP00000369442.3		Q9UEF7-1
KL	ENST00000487852.1 link	n.828-144A>G		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.266

AC:

40403

AN:

151994

Hom.:

5838

Cov.:

show subpopulations

Gnomad AFR

AF:

0.200

Gnomad AMI

AF:

0.356

Gnomad AMR

AF:

0.215

Gnomad ASJ

AF:

0.260

Gnomad EAS

AF:

0.451

Gnomad SAS

AF:

0.331

Gnomad FIN

AF:

0.306

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.291

Gnomad OTH

AF:

0.286

GnomAD4 exome

AF:

0.295

AC:

183967

AN:

622880

Hom.:

28122

AF XY:

0.296

AC XY:

96030

AN XY:

324506

show subpopulations

Gnomad4 AFR exome

AF:

0.201

Gnomad4 AMR exome

AF:

0.178

Gnomad4 ASJ exome

AF:

0.261

Gnomad4 EAS exome

AF:

0.462

Gnomad4 SAS exome

AF:

0.301

Gnomad4 FIN exome

AF:

0.292

Gnomad4 NFE exome

AF:

0.295

Gnomad4 OTH exome

AF:

0.282

GnomAD4 genome

AF:

0.266

AC:

40420

AN:

152110

Hom.:

5842

Cov.:

AF XY:

0.268

AC XY:

19904

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.200

Gnomad4 AMR

AF:

0.215

Gnomad4 ASJ

AF:

0.260

Gnomad4 EAS

AF:

0.451

Gnomad4 SAS

AF:

0.331

Gnomad4 FIN

AF:

0.306

Gnomad4 NFE

AF:

0.291

Gnomad4 OTH

AF:

0.283

Alfa

AF:

0.265

Hom.:

781

Bravo

AF:

0.257

Asia WGS

AF:

0.347

AC:

1206

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.9

DANN

Benign

0.54

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over