rs1004673

Variant names:

• chr5-14840826-G-C
• rs1004673
• NM_054027.6:c.96+30526C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-14840826-G-C
• chr5-14840826-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

ANKH Gene-Disease associations (from GenCC):

• chondrocalcinosis 2

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
• craniometaphyseal dysplasia, autosomal dominant

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
• skeletal dysplasia

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• craniometaphyseal dysplasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_054027.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKH	NM_054027.6	MANE Select	c.96+30526C>G		intron	N/A	NP_473368.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKH	ENST00000284268.8	TSL:1 MANE Select	c.96+30526C>G		intron	N/A	ENSP00000284268.6
	ANKH	ENST00000513115.1	TSL:2	n.121+30526C>G		intron	N/A

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

African (AFR) AF: 0.357 AC: 14778 AN: 41440

American (AMR) AF: 0.398 AC: 6080 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1208 AN: 3472

East Asian (EAS) AF: 0.307 AC: 1588 AN: 5170

South Asian (SAS) AF: 0.292 AC: 1408 AN: 4818

European-Finnish (FIN) AF: 0.314 AC: 3311 AN: 10534

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23429 AN: 67986

Other (OTH) AF: 0.304 AC: 643 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.2
DANN	Benign	0.70
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1004673; hg19: chr5-14840935;