chr5-14751291-T-C

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

2

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]

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 HGVSp Effect #exon/exons MANE UniProt
ANKHNM_054027.6 linkuse as main transcriptc.517-52A>G intron_variant ENST00000284268.8
ANKHXM_011514067.2 linkuse as main transcriptc.517-52A>G intron_variant
ANKHXM_017009644.3 linkuse as main transcriptc.433-52A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ANKHENST00000284268.8 linkuse as main transcriptc.517-52A>G intron_variant 1 NM_054027.6 P1Q9HCJ1-1
ANKHENST00000503939.5 linkuse as main transcriptn.29-52A>G intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.171
AC:
25944
AN:
152054
Hom.:
4167
Cov.:
33
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.:
24
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.:
33
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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxNov 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.

Other links and lift over

dbSNP: rs2291943; hg19: chr5-14751400; COSMIC: COSV52478581; COSMIC: COSV52478581; API