chr5-14751479-T-G

Position:

• chr5-14751479-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_054027.6(ANKH):​c.517-240A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,184 control chromosomes in the GnomAD database, including 5,372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.25 (5372 hom., cov: 33)
• Consequence: ANKH NM_054027.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.53

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 5-14751479-T-G is Benign according to our data. Variant chr5-14751479-T-G is described in ClinVar as [Benign]. Clinvar id is 1261660.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKH	NM_054027.6	c.517-240A>C		intron_variant		ENST00000284268.8	NP_473368.1
ANKH	XM_011514067.2	c.517-240A>C		intron_variant			XP_011512369.1
ANKH	XM_017009644.3	c.433-240A>C		intron_variant			XP_016865133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKH	ENST00000284268.8	c.517-240A>C		intron_variant		1	NM_054027.6	ENSP00000284268	P1
ANKH	ENST00000503939.5	n.29-240A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38627 AN: 152066 Hom.: 5366 Cov.: 33

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0797

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.254 AC: 38667 AN: 152184 Hom.: 5372 Cov.: 33 AF XY: 0.251 AC XY: 18695 AN XY: 74410

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.0800

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.252

Alfa AF: 0.160 Hom.: 419

Bravo AF: 0.272

Asia WGS AF: 0.123 AC: 433 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.039
DANN	Benign	0.43

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: rs697571; hg19: chr5-14751588;