rs2921600

Positions:

• chr5-14860614-G-A
• chr5-14860614-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+10738C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 151,944 control chromosomes in the GnomAD database, including 36,879 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 (36879 hom., cov: 32)
• Consequence: ANKH NM_054027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKH	NM_054027.6	c.96+10738C>T		intron_variant		ENST00000284268.8
ANKH	XM_011514067.2	c.96+10738C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKH	ENST00000284268.8	c.96+10738C>T		intron_variant		1	NM_054027.6	P1
ANKH	ENST00000513115.1	n.121+10738C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105140 AN: 151826 Hom.: 36888 Cov.: 32

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.888

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.841

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.715

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

GnomAD4 genome AF: 0.692 AC: 105159 AN: 151944 Hom.: 36879 Cov.: 32 AF XY: 0.689 AC XY: 51198 AN XY: 74264

Gnomad4 AFR AF: 0.609

Gnomad4 AMR AF: 0.686

Gnomad4 ASJ AF: 0.826

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.665

Gnomad4 FIN AF: 0.745

Gnomad4 NFE AF: 0.746

Gnomad4 OTH AF: 0.705

Alfa AF: 0.735 Hom.: 83428

Bravo AF: 0.682

Asia WGS AF: 0.525 AC: 1831 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.36
DANN	Benign	0.66

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: rs2921600; hg19: chr5-14860723;