5-14790041-G-C

Position:

• chr5-14790041-G-C

Variant summary

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

The NM_054027.6(ANKH):​c.97-20850C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 152,144 control chromosomes in the GnomAD database, including 44,138 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 0.76 (44138 hom., cov: 33)
• Consequence: ANKH NM_054027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKH	NM_054027.6	c.97-20850C>G		intron_variant		ENST00000284268.8	NP_473368.1
ANKH	XM_017009644.3	c.12+6177C>G		intron_variant			XP_016865133.1
ANKH	XM_011514067.2	c.97-20850C>G		intron_variant			XP_011512369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKH	ENST00000284268.8	c.97-20850C>G		intron_variant		1	NM_054027.6	ENSP00000284268.6
ANKH	ENST00000513115.1	n.122-20850C>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115603 AN: 152026 Hom.: 44082 Cov.: 33

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.753

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

GnomAD4 genome AF: 0.761 AC: 115720 AN: 152144 Hom.: 44138 Cov.: 33 AF XY: 0.765 AC XY: 56934 AN XY: 74404

Gnomad4 AFR AF: 0.719

Gnomad4 AMR AF: 0.804

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.840

Gnomad4 SAS AF: 0.856

Gnomad4 FIN AF: 0.799

Gnomad4 NFE AF: 0.762

Gnomad4 OTH AF: 0.756

Alfa AF: 0.772 Hom.: 5334

Bravo AF: 0.754

Asia WGS AF: 0.838 AC: 2915 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.22
DANN	Benign	0.44

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: rs258231; hg19: chr5-14790150;