rs4701616

chr5-14760498-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.314-1900G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,124 control chromosomes in the GnomAD database, including 36,759 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 0.69 (36759 hom., cov: 32)
• Consequence: ANKH NM_054027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKH	NM_054027.6	c.314-1900G>A		intron_variant		ENST00000284268.8
ANKH	XM_011514067.2	c.314-1900G>A		intron_variant
ANKH	XM_017009644.3	c.230-1900G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKH	ENST00000284268.8	c.314-1900G>A		intron_variant		1	NM_054027.6	P1

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104516 AN: 152006 Hom.: 36703 Cov.: 32

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.685

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

GnomAD4 genome AF: 0.688 AC: 104624 AN: 152124 Hom.: 36759 Cov.: 32 AF XY: 0.683 AC XY: 50811 AN XY: 74374

Gnomad4 AFR AF: 0.820

Gnomad4 AMR AF: 0.717

Gnomad4 ASJ AF: 0.617

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.647

Gnomad4 OTH AF: 0.677

Alfa AF: 0.657 Hom.: 46970

Bravo AF: 0.698

Asia WGS AF: 0.487 AC: 1696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.25
Dann	Benign	0.79

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: rs4701616; hg19: chr5-14760607;