rs1061813

Positions:

• chr5-14847222-G-A
• chr5-14847222-G-C
• chr5-14847222-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.96+24130C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 151,790 control chromosomes in the GnomAD database, including 23,847 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 0.55 (23847 hom., cov: 30)
• Consequence: ANKH NM_054027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKH	NM_054027.6	c.96+24130C>T		intron_variant		ENST00000284268.8	NP_473368.1
ANKH	XM_011514067.2	c.96+24130C>T		intron_variant			XP_011512369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKH	ENST00000284268.8	c.96+24130C>T		intron_variant		1	NM_054027.6	ENSP00000284268	P1
ANKH	ENST00000513115.1	n.121+24130C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84099 AN: 151672 Hom.: 23803 Cov.: 30

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.549

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.555 AC: 84201 AN: 151790 Hom.: 23847 Cov.: 30 AF XY: 0.562 AC XY: 41676 AN XY: 74162

Gnomad4 AFR AF: 0.469

Gnomad4 AMR AF: 0.652

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.839

Gnomad4 SAS AF: 0.676

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.549

Gnomad4 OTH AF: 0.519

Alfa AF: 0.563 Hom.: 3028

Bravo AF: 0.550

Asia WGS AF: 0.755 AC: 2626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.13
DANN	Benign	0.21

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: rs1061813; hg19: chr5-14847331;