rs696294

Positions:

• chr5-14735006-A-G

Variant summary

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

The NM_054027.6(ANKH):​c.1011+6821T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,078 control chromosomes in the GnomAD database, including 9,225 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 0.32 (9225 hom., cov: 32)
• Consequence: ANKH NM_054027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.533

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]

LOC124900944 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKH	NM_054027.6	c.1011+6821T>C		intron_variant		ENST00000284268.8	NP_473368.1
LOC124900944	XR_007058699.1	n.10657A>G		non_coding_transcript_exon_variant	2/2
ANKH	XM_017009644.3	c.927+6821T>C		intron_variant			XP_016865133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKH	ENST00000284268.8	c.1011+6821T>C		intron_variant		1	NM_054027.6	ENSP00000284268	P1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48358 AN: 151960 Hom.: 9204 Cov.: 32

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.318 AC: 48420 AN: 152078 Hom.: 9225 Cov.: 32 AF XY: 0.311 AC XY: 23137 AN XY: 74346

Gnomad4 AFR AF: 0.545

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.305

Alfa AF: 0.250 Hom.: 2894

Bravo AF: 0.337

Asia WGS AF: 0.148 AC: 518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.68
DANN	Benign	0.47

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: rs696294; hg19: chr5-14735115;