rs211234

Variant names:

• chr13-33020990-G-A
• rs211234
• NM_004795.4:c.819+3731G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-33020990-G-A
• chr13-33020990-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004795.4(KL):​c.819+3731G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 151,932 control chromosomes in the GnomAD database, including 8,777 homozygotes. 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 0.32 (8777 hom., cov: 32)
• Consequence: KL NM_004795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.317
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• tumoral calcinosis, hyperphosphatemic, familial, 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• tumoral calcinosis, hyperphosphatemic, familial, 3

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KL	NM_004795.4	c.819+3731G>A		intron_variant	Intron 1 of 4	ENST00000380099.4	NP_004786.2
KL	XM_006719895.3	c.-103+4677G>A		intron_variant	Intron 1 of 4		XP_006719958.1
KL	XM_047430775.1	c.819+3731G>A		intron_variant	Intron 1 of 3		XP_047286731.1
KL	XM_047430776.1	c.819+3731G>A		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	c.819+3731G>A		intron_variant	Intron 1 of 4	1	NM_004795.4	ENSP00000369442.3
KL	ENST00000487852.1	n.827+3731G>A		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.316 AC: 48035 AN: 151814 Hom.: 8767 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.338

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.316 AC: 48058 AN: 151932 Hom.: 8777 Cov.: 32 AF XY: 0.316 AC XY: 23456 AN XY: 74252

African (AFR) AF: 0.150 AC: 6216 AN: 41438

American (AMR) AF: 0.438 AC: 6682 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1275 AN: 3472

East Asian (EAS) AF: 0.161 AC: 830 AN: 5152

South Asian (SAS) AF: 0.241 AC: 1158 AN: 4798

European-Finnish (FIN) AF: 0.379 AC: 4003 AN: 10560

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26704 AN: 67924

Other (OTH) AF: 0.342 AC: 722 AN: 2114

Alfa AF: 0.334 Hom.: 3088

Bravo AF: 0.317

Asia WGS AF: 0.252 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.78
PhyloP100		-0.32
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: rs211234; hg19: chr13-33595128;