rs1004673

chr5-14840826-G-Cchr5-14840826-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+30526C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,018 control chromosomes in the GnomAD database, including 9,252 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 0.35 (9252 hom., cov: 32)
• Consequence: ANKH NM_054027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.358

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKH	NM_054027.6	c.96+30526C>G		intron_variant		ENST00000284268.8
ANKH	XM_011514067.2	c.96+30526C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKH	ENST00000284268.8	c.96+30526C>G		intron_variant		1	NM_054027.6	P1
ANKH	ENST00000513115.1	n.121+30526C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52828 AN: 151900 Hom.: 9232 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.348 AC: 52896 AN: 152018 Hom.: 9252 Cov.: 32 AF XY: 0.344 AC XY: 25547 AN XY: 74298

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.304

Alfa AF: 0.237 Hom.: 571

Bravo AF: 0.352

Asia WGS AF: 0.302 AC: 1051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	9.2
Dann	Benign	0.70

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: rs1004673; hg19: chr5-14840935;