rs1061813

Variant names:

• chr5-14847222-G-A
• rs1061813
• NM_054027.6:c.96+24130C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-14847222-G-A
• chr5-14847222-G-C
• chr5-14847222-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+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
• Publications: 6 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=-0.97).
• 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 rank	MANE	Protein	UniProt
ANKH	NM_054027.6	c.96+24130C>T		intron_variant	Intron 1 of 11	ENST00000284268.8	NP_473368.1
ANKH	XM_011514067.2	c.96+24130C>T		intron_variant	Intron 1 of 8		XP_011512369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKH	ENST00000284268.8	c.96+24130C>T		intron_variant	Intron 1 of 11	1	NM_054027.6	ENSP00000284268.6
ANKH	ENST00000513115.1	n.121+24130C>T		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.469 AC: 19392 AN: 41364

American (AMR) AF: 0.652 AC: 9944 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1797 AN: 3466

East Asian (EAS) AF: 0.839 AC: 4333 AN: 5164

South Asian (SAS) AF: 0.676 AC: 3248 AN: 4806

European-Finnish (FIN) AF: 0.619 AC: 6512 AN: 10518

Middle Eastern (MID) AF: 0.452 AC: 132 AN: 292

European-Non Finnish (NFE) AF: 0.549 AC: 37313 AN: 67928

Other (OTH) AF: 0.519 AC: 1089 AN: 2100

Alfa AF: 0.562 Hom.: 3137

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
PhyloP100		-1.4
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: rs1061813; hg19: chr5-14847331;