5-14797551-A-G

Position:

• chr5-14797551-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_054027.6(ANKH):​c.97-28360T>C variant causes a intron change. The variant allele was found at a frequency of 0.491 in 1,610,676 control chromosomes in the GnomAD database, including 198,323 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 0.50 (19285 hom., cov: 32)
  • Exomes 𝑓: 0.49 (179038 hom.)
• Consequence: ANKH NM_054027.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.67

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]

RBBP4P1 (HGNC:42368): (RBBP4 pseudogene 1)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKH	NM_054027.6	c.97-28360T>C		intron_variant		ENST00000284268.8
ANKH	XM_017009644.3	c.-1322T>C		5_prime_UTR_variant	1/12
ANKH	XM_011514067.2	c.97-28360T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKH	ENST00000284268.8	c.97-28360T>C		intron_variant		1	NM_054027.6	P1
RBBP4P1	ENST00000502424.1	n.850T>C		non_coding_transcript_exon_variant	1/1
ANKH	ENST00000513115.1	n.122-28360T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75997 AN: 151928 Hom.: 19244 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.462

GnomAD4 exome AF: 0.490 AC: 714605 AN: 1458630 Hom.: 179038 Cov.: 56 AF XY: 0.493 AC XY: 357717 AN XY: 725714

Gnomad4 AFR exome AF: 0.508

Gnomad4 AMR exome AF: 0.595

Gnomad4 ASJ exome AF: 0.469

Gnomad4 EAS exome AF: 0.796

Gnomad4 SAS exome AF: 0.611

Gnomad4 FIN exome AF: 0.438

Gnomad4 NFE exome AF: 0.468

Gnomad4 OTH exome AF: 0.492

GnomAD4 genome AF: 0.500 AC: 76094 AN: 152046 Hom.: 19285 Cov.: 32 AF XY: 0.503 AC XY: 37376 AN XY: 74316

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.752

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.469

Alfa AF: 0.491 Hom.: 2617

Bravo AF: 0.506

Asia WGS AF: 0.697 AC: 2423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	7.6
DANN	Benign	0.91

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: rs31989; hg19: chr5-14797660;