rs17250963

chr5-14752741-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_054027.6(ANKH):c.517-1502C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 151,798 control chromosomes in the GnomAD database, including 2,749 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 0.18 (2749 hom., cov: 32)
• Consequence: ANKH NM_054027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.485

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKH	NM_054027.6	c.517-1502C>T		intron_variant		ENST00000284268.8
ANKH	XM_011514067.2	c.517-1502C>T		intron_variant
ANKH	XM_017009644.3	c.433-1502C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKH	ENST00000284268.8	c.517-1502C>T		intron_variant		1	NM_054027.6	P1
ANKH	ENST00000503939.5	n.29-1502C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27883 AN: 151682 Hom.: 2748 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.000777

Gnomad SAS AF: 0.0360

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.184 AC: 27895 AN: 151798 Hom.: 2749 Cov.: 32 AF XY: 0.180 AC XY: 13341 AN XY: 74198

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.000779

Gnomad4 SAS AF: 0.0356

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.195

Alfa AF: 0.185 Hom.: 2857

Bravo AF: 0.187

Asia WGS AF: 0.0380 AC: 135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.5
Dann	Benign	0.60

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

Other links and lift over

dbSNP: rs17250963; hg19: chr5-14752850;