rs744165

Variant names:

• chr5-14763598-C-A
• rs744165
• NM_054027.6:c.314-5000G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-14763598-C-A
• chr5-14763598-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_054027.6(ANKH):​c.314-5000G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,060 control chromosomes in the GnomAD database, including 8,928 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 0.34 (8928 hom., cov: 33)
• Consequence: ANKH NM_054027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKH	NM_054027.6	c.314-5000G>T		intron_variant	Intron 2 of 11	ENST00000284268.8	NP_473368.1
ANKH	XM_017009644.3	c.230-5000G>T		intron_variant	Intron 2 of 11		XP_016865133.1
ANKH	XM_011514067.2	c.314-5000G>T		intron_variant	Intron 2 of 8		XP_011512369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKH	ENST00000284268.8	c.314-5000G>T		intron_variant	Intron 2 of 11	1	NM_054027.6	ENSP00000284268.6

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51827 AN: 151942 Hom.: 8922 Cov.: 33

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.341 AC: 51853 AN: 152060 Hom.: 8928 Cov.: 33 AF XY: 0.342 AC XY: 25380 AN XY: 74302

African (AFR) AF: 0.315 AC: 13040 AN: 41450

American (AMR) AF: 0.293 AC: 4484 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1181 AN: 3468

East Asian (EAS) AF: 0.399 AC: 2068 AN: 5180

South Asian (SAS) AF: 0.300 AC: 1445 AN: 4822

European-Finnish (FIN) AF: 0.420 AC: 4424 AN: 10540

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24295 AN: 67986

Other (OTH) AF: 0.333 AC: 703 AN: 2114

Alfa AF: 0.344 Hom.: 11675

Bravo AF: 0.333

Asia WGS AF: 0.341 AC: 1184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.41
PhyloP100		-1.0
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: rs744165; hg19: chr5-14763707;