rs744165

Positions:

• chr5-14763598-C-A
• chr5-14763598-C-G

Variant summary

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

The NM_054027.6(ANKH):​c.314-5000G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,060 control chromosomes in the GnomAD database, including 8,928 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 0.34 (8928 hom., cov: 33)
• Consequence: ANKH NM_054027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKH	NM_054027.6	c.314-5000G>T		intron_variant		ENST00000284268.8	NP_473368.1
ANKH	XM_011514067.2	c.314-5000G>T		intron_variant			XP_011512369.1
ANKH	XM_017009644.3	c.230-5000G>T		intron_variant			XP_016865133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKH	ENST00000284268.8	c.314-5000G>T		intron_variant		1	NM_054027.6	ENSP00000284268	P1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51827 AN: 151942 Hom.: 8922 Cov.: 33

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.341 AC: 51853 AN: 152060 Hom.: 8928 Cov.: 33 AF XY: 0.342 AC XY: 25380 AN XY: 74302

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.333

Alfa AF: 0.345 Hom.: 8906

Bravo AF: 0.333

Asia WGS AF: 0.341 AC: 1184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.41

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: rs744165; hg19: chr5-14763707;