rs6425513

Variant names:

• chr1-179037327-G-A
• rs6425513
• NM_014864.4:c.-133-6388G>A

Variant summary

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

The NM_014864.4(FAM20B):​c.-133-6388G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 151,788 control chromosomes in the GnomAD database, including 39,493 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 0.71 (39493 hom., cov: 29)
• Consequence: FAM20B NM_014864.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 7 publications found

Genes affected

FAM20B (HGNC:23017): (FAM20B glycosaminoglycan xylosylkinase) Enables phosphotransferase activity, alcohol group as acceptor. Predicted to be involved in proteoglycan biosynthetic process. Located in Golgi apparatus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FAM20B Gene-Disease associations (from GenCC):

• Desbuquois dysplasia

  Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM20B	NM_014864.4	c.-133-6388G>A		intron_variant	Intron 1 of 7	ENST00000263733.5	NP_055679.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM20B	ENST00000263733.5	c.-133-6388G>A		intron_variant	Intron 1 of 7	1	NM_014864.4	ENSP00000263733.4
FAM20B	ENST00000440702.5	c.-133-6388G>A		intron_variant	Intron 1 of 2	3		ENSP00000404005.1

Frequencies

GnomAD3 genomes AF: 0.711 AC: 107770 AN: 151672 Hom.: 39444 Cov.: 29

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.711 AC: 107877 AN: 151788 Hom.: 39493 Cov.: 29 AF XY: 0.711 AC XY: 52717 AN XY: 74140

African (AFR) AF: 0.886 AC: 36680 AN: 41396

American (AMR) AF: 0.592 AC: 9044 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2404 AN: 3468

East Asian (EAS) AF: 0.595 AC: 3068 AN: 5152

South Asian (SAS) AF: 0.604 AC: 2894 AN: 4792

European-Finnish (FIN) AF: 0.754 AC: 7913 AN: 10492

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.643 AC: 43697 AN: 67906

Other (OTH) AF: 0.708 AC: 1493 AN: 2110

Alfa AF: 0.661 Hom.: 129208

Bravo AF: 0.707

Asia WGS AF: 0.676 AC: 2352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.11
DANN	Benign	0.51
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: rs6425513; hg19: chr1-179006462;