rs2454873

Positions:

• chr5-14765078-G-A
• chr5-14765078-G-C
• chr5-14765078-G-T

Variant summary

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

The NM_054027.6(ANKH):​c.313+3897C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 152,166 control chromosomes in the GnomAD database, including 6,224 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 0.28 (6224 hom., cov: 33)
• Consequence: ANKH NM_054027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKH	NM_054027.6	c.313+3897C>T		intron_variant		ENST00000284268.8
ANKH	XM_011514067.2	c.313+3897C>T		intron_variant
ANKH	XM_017009644.3	c.229+3897C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKH	ENST00000284268.8	c.313+3897C>T		intron_variant		1	NM_054027.6	P1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43143 AN: 152048 Hom.: 6222 Cov.: 33

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.284 AC: 43162 AN: 152166 Hom.: 6224 Cov.: 33 AF XY: 0.282 AC XY: 21008 AN XY: 74390

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.253

Alfa AF: 0.263 Hom.: 2519

Bravo AF: 0.285

Asia WGS AF: 0.273 AC: 949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.7
DANN	Benign	0.76

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: rs2454873; hg19: chr5-14765187;