Genetic Variant ANKH:c.97-28360T>C (chr5-14797551-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_054027.6(ANKH):c.97-28360T>C variant causes a intron change. The variant allele was found at a frequency of 0.491 in 1,610,676 control chromosomes in the GnomAD database, including 198,323 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 0.50 ( 19285 hom., cov: 32)

Exomes 𝑓: 0.49 ( 179038 hom. )

Consequence

ANKH
NM_054027.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.67

Publications

3 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 links:

RBBP4P1 (HGNC:42368): (RBBP4 pseudogene 1)

RBBP4P1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_054027.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKH	NM_054027.6	MANE Select	c.97-28360T>C		intron	N/A	NP_473368.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ANKH	ENST00000284268.8	TSL:1 MANE Select	c.97-28360T>C	intron	N/A	ENSP00000284268.6
ANKH	ENST00000887636.1		c.97-28360T>C	intron	N/A	ENSP00000557695.1
ANKH	ENST00000964374.1		c.97-28360T>C	intron	N/A	ENSP00000634433.1

Frequencies

GnomAD3 genomes

AF:

0.500

AC:

75997

AN:

151928

Hom.:

19244

Cov.:

show subpopulations

Gnomad AFR

AF:

0.510

Gnomad AMI

AF:

0.447

Gnomad AMR

AF:

0.560

Gnomad ASJ

AF:

0.468

Gnomad EAS

AF:

0.753

Gnomad SAS

AF:

0.627

Gnomad FIN

AF:

0.419

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.469

Gnomad OTH

AF:

0.462

GnomAD4 exome

AF:

0.490

AC:

714605

AN:

1458630

Hom.:

179038

Cov.:

AF XY:

0.493

AC XY:

357717

AN XY:

725714

show subpopulations

African (AFR)

AF:

0.508

AC:

16972

AN:

33390

American (AMR)

AF:

0.595

AC:

26617

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.469

AC:

12254

AN:

26120

East Asian (EAS)

AF:

0.796

AC:

31614

AN:

39700

South Asian (SAS)

AF:

0.611

AC:

52596

AN:

86134

European-Finnish (FIN)

AF:

0.438

AC:

23393

AN:

53416

Middle Eastern (MID)

AF:

0.422

AC:

1747

AN:

4136

European-Non Finnish (NFE)

AF:

0.468

AC:

519787

AN:

1110832

Other (OTH)

AF:

0.492

AC:

29625

AN:

60186

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

22718

45436

68153

90871

113589

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15610

31220

46830

62440

78050

<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:

0.500

AC:

76094

AN:

152046

Hom.:

19285

Cov.:

AF XY:

0.503

AC XY:

37376

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.510

AC:

21133

AN:

41442

American (AMR)

AF:

0.561

AC:

8572

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.468

AC:

1624

AN:

3470

East Asian (EAS)

AF:

0.752

AC:

3895

AN:

5178

South Asian (SAS)

AF:

0.629

AC:

3030

AN:

4820

European-Finnish (FIN)

AF:

0.419

AC:

4422

AN:

10564

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.469

AC:

31896

AN:

67966

Other (OTH)

AF:

0.469

AC:

989

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1969

3938

5907

7876

9845

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

680

1360

2040

2720

3400

<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:

0.491

Hom.:

2617

Bravo

AF:

0.506

Asia WGS

AF:

0.697

AC:

2423

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

7.6

(source)

DANN

Benign

0.91

PhyloP100

6.7

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

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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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over