dbSNP rs258215: ANKH:c.314-4829A>T (chr5-14763427-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_054027.6(ANKH):c.314-4829A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 152,050 control chromosomes in the GnomAD database, including 31,161 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 0.64 ( 31161 hom., cov: 33)

Consequence

ANKH
NM_054027.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.33

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

chondrocalcinosis 2
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
craniometaphyseal dysplasia, autosomal dominant
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
skeletal dysplasia
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
craniometaphyseal dysplasia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ANKH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ANKH	NM_054027.6 link	c.314-4829A>T	intron_variant	Intron 2 of 11	ENST00000284268.8	NP_473368.1	Q9HCJ1-1
ANKH	XM_017009644.3 link	c.230-4829A>T	intron_variant	Intron 2 of 11		XP_016865133.1
ANKH	XM_011514067.2 link	c.314-4829A>T	intron_variant	Intron 2 of 8		XP_011512369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKH	ENST00000284268.8 link	c.314-4829A>T		intron_variant	Intron 2 of 11	1	NM_054027.6	ENSP00000284268.6		Q9HCJ1-1

Frequencies

GnomAD3 genomes

AF:

0.636

AC:

96620

AN:

151932

Hom.:

31111

Cov.:

show subpopulations

Gnomad AFR

AF:

0.724

Gnomad AMI

AF:

0.670

Gnomad AMR

AF:

0.657

Gnomad ASJ

AF:

0.618

Gnomad EAS

AF:

0.409

Gnomad SAS

AF:

0.648

Gnomad FIN

AF:

0.544

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.609

Gnomad OTH

AF:

0.620

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

GnomAD4 genome

AF:

0.636

AC:

96725

AN:

152050

Hom.:

31161

Cov.:

AF XY:

0.633

AC XY:

47014

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.724

AC:

30039

AN:

41478

American (AMR)

AF:

0.657

AC:

10048

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.618

AC:

2147

AN:

3472

East Asian (EAS)

AF:

0.408

AC:

2107

AN:

5164

South Asian (SAS)

AF:

0.650

AC:

3126

AN:

4812

European-Finnish (FIN)

AF:

0.544

AC:

5749

AN:

10568

Middle Eastern (MID)

AF:

0.588

AC:

173

AN:

294

European-Non Finnish (NFE)

AF:

0.609

AC:

41419

AN:

67958

Other (OTH)

AF:

0.619

AC:

1307

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1834

3669

5503

7338

9172

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

788

1576

2364

3152

3940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.638

Hom.:

3843

Bravo

AF:

0.643

Asia WGS

AF:

0.570

AC:

1983

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.047

(source)

DANN

Benign

0.47

PhyloP100

-3.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over