rs706293

Positions:

• chr5-14764825-G-A

Variant summary

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

The ENST00000284268.8(ANKH):​c.313+4150C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 152,108 control chromosomes in the GnomAD database, including 13,207 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 0.41 (13207 hom., cov: 33)
• Consequence: ANKH ENST00000284268.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKH	NM_054027.6	c.313+4150C>T		intron_variant		ENST00000284268.8	NP_473368.1
ANKH	XM_011514067.2	c.313+4150C>T		intron_variant			XP_011512369.1
ANKH	XM_017009644.3	c.229+4150C>T		intron_variant			XP_016865133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKH	ENST00000284268.8	c.313+4150C>T		intron_variant		1	NM_054027.6	ENSP00000284268	P1

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63039 AN: 151990 Hom.: 13192 Cov.: 33

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.415 AC: 63094 AN: 152108 Hom.: 13207 Cov.: 33 AF XY: 0.416 AC XY: 30936 AN XY: 74350

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.357

Alfa AF: 0.382 Hom.: 22774

Bravo AF: 0.415

Asia WGS AF: 0.352 AC: 1222 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.67

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: rs706293; hg19: chr5-14764934;