rs4702049

chr5-14759137-C-T

Variant summary

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

The NM_054027.6(ANKH):c.314-539G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 152,054 control chromosomes in the GnomAD database, including 11,490 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 0.38 (11490 hom., cov: 32)
• Consequence: ANKH NM_054027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.444

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKH	NM_054027.6	c.314-539G>A		intron_variant		ENST00000284268.8
ANKH	XM_011514067.2	c.314-539G>A		intron_variant
ANKH	XM_017009644.3	c.230-539G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKH	ENST00000284268.8	c.314-539G>A		intron_variant		1	NM_054027.6	P1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58485 AN: 151934 Hom.: 11475 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.385 AC: 58536 AN: 152054 Hom.: 11490 Cov.: 32 AF XY: 0.385 AC XY: 28633 AN XY: 74306

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.342

Alfa AF: 0.383 Hom.: 17745

Bravo AF: 0.390

Asia WGS AF: 0.319 AC: 1108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.9
Dann	Benign	0.66

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: rs4702049; hg19: chr5-14759246;