rs6425512

Variant names:

• chr1-179031008-G-A
• rs6425512
• NM_014864.4:c.-134+4910G>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.-134+4910G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 152,094 control chromosomes in the GnomAD database, including 46,119 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 0.77 (46119 hom., cov: 31)
• Consequence: FAM20B NM_014864.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161
• Publications: 3 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):

• congenital disorder of glycosylation

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014864.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM20B	NM_014864.4	MANE Select	c.-134+4910G>A		intron	N/A	NP_055679.1	O75063
	FAM20B	NM_001324310.2		c.-134+5150G>A		intron	N/A	NP_001311239.1	O75063
	FAM20B	NM_001324311.2		c.-134+4820G>A		intron	N/A	NP_001311240.1	O75063

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM20B	ENST00000263733.5	TSL:1 MANE Select	c.-134+4910G>A		intron	N/A	ENSP00000263733.4	O75063
	FAM20B	ENST00000889611.1		c.-134+4178G>A		intron	N/A	ENSP00000559670.1
	FAM20B	ENST00000929138.1		c.-134+4820G>A		intron	N/A	ENSP00000599197.1

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117147 AN: 151976 Hom.: 46073 Cov.: 31

Gnomad AFR AF: 0.931

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.798

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.804

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.759

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

GnomAD4 genome AF: 0.771 AC: 117246 AN: 152094 Hom.: 46119 Cov.: 31 AF XY: 0.774 AC XY: 57499 AN XY: 74330

African (AFR) AF: 0.930 AC: 38620 AN: 41514

American (AMR) AF: 0.691 AC: 10554 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.798 AC: 2770 AN: 3472

East Asian (EAS) AF: 0.646 AC: 3342 AN: 5170

South Asian (SAS) AF: 0.717 AC: 3461 AN: 4828

European-Finnish (FIN) AF: 0.804 AC: 8471 AN: 10538

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47682 AN: 67986

Other (OTH) AF: 0.762 AC: 1606 AN: 2108

Alfa AF: 0.723 Hom.: 20428

Bravo AF: 0.767

Asia WGS AF: 0.757 AC: 2635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.1
DANN	Benign	0.42
PhyloP100		-0.16
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: rs6425512; hg19: chr1-179000143;