Variant rs2291943 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_054027.6(ANKH):c.517-52A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0812 in 1,575,912 control chromosomes in the GnomAD database, including 11,367 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 4198 hom., cov: 33)

Exomes 𝑓: 0.072 ( 7169 hom. )

Consequence

ANKH
NM_054027.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.70

Variant links:

Genes affected

ANKH (HGNC:15492): (ANKH inorganic pyrophosphate transport regulator) This gene encodes a multipass transmembrane protein that is expressed in joints and other tissues and controls pyrophosphate levels in cultured cells. Progressive ankylosis-mediated control of pyrophosphate levels has been suggested as a possible mechanism regulating tissue calcification and susceptibility to arthritis in higher animals. Mutations in this gene have been associated with autosomal dominant craniometaphyseal dysplasia. [provided by RefSeq, Jul 2008]

ANKH 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=-0.94).

BP6

Variant 5-14751291-T-C is Benign according to our data. Variant chr5-14751291-T-C is described in ClinVar as [Benign]. Clinvar id is 1238126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ANKH	NM_054027.6 linkuse as main transcript	c.517-52A>G	intron_variant	ENST00000284268.8
ANKH	XM_011514067.2 linkuse as main transcript	c.517-52A>G	intron_variant
ANKH	XM_017009644.3 linkuse as main transcript	c.433-52A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKH	ENST00000284268.8 linkuse as main transcript	c.517-52A>G		intron_variant		1	NM_054027.6	P1	Q9HCJ1-1
ANKH	ENST00000503939.5 linkuse as main transcript	n.29-52A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

25944

AN:

152054

Hom.:

4167

Cov.:

show subpopulations

Gnomad AFR

AF:

0.418

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.199

Gnomad ASJ

AF:

0.0737

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.0596

Gnomad FIN

AF:

0.0468

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0543

Gnomad OTH

AF:

0.132

GnomAD3 exomes

AF:

0.115

AC:

27890

AN:

241628

Hom.:

3221

AF XY:

0.0996

AC XY:

13029

AN XY:

130864

show subpopulations

Gnomad AFR exome

AF:

0.428

Gnomad AMR exome

AF:

0.291

Gnomad ASJ exome

AF:

0.0687

Gnomad EAS exome

AF:

0.105

Gnomad SAS exome

AF:

0.0551

Gnomad FIN exome

AF:

0.0428

Gnomad NFE exome

AF:

0.0542

Gnomad OTH exome

AF:

0.0841

GnomAD4 exome

AF:

0.0716

AC:

101959

AN:

1423740

Hom.:

7169

Cov.:

AF XY:

0.0690

AC XY:

48967

AN XY:

709966

show subpopulations

Gnomad4 AFR exome

AF:

0.430

Gnomad4 AMR exome

AF:

0.278

Gnomad4 ASJ exome

AF:

0.0736

Gnomad4 EAS exome

AF:

0.105

Gnomad4 SAS exome

AF:

0.0550

Gnomad4 FIN exome

AF:

0.0445

Gnomad4 NFE exome

AF:

0.0532

Gnomad4 OTH exome

AF:

0.0831

GnomAD4 genome

AF:

0.171

AC:

26035

AN:

152172

Hom.:

4198

Cov.:

AF XY:

0.169

AC XY:

12549

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.419

Gnomad4 AMR

AF:

0.200

Gnomad4 ASJ

AF:

0.0737

Gnomad4 EAS

AF:

0.101

Gnomad4 SAS

AF:

0.0597

Gnomad4 FIN

AF:

0.0468

Gnomad4 NFE

AF:

0.0543

Gnomad4 OTH

AF:

0.131

Alfa

AF:

0.0822

Hom.:

1143

Bravo

AF:

0.197

Asia WGS

AF:

0.111

AC:

387

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.22

DANN

Benign

0.35

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