rs4962683

chr10-124683388-C-T

Variant summary

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

The NM_014661.4(FAM53B):c.134-1009G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,108 control chromosomes in the GnomAD database, including 6,397 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 0.27 (6397 hom., cov: 33)
• Consequence: FAM53B NM_014661.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58

Genes affected

FAM53B (HGNC:28968): (family with sequence similarity 53 member B) Involved in positive regulation of canonical Wnt signaling pathway. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM53B	NM_014661.4	c.134-1009G>A		intron_variant		ENST00000337318.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM53B	ENST00000337318.8	c.134-1009G>A		intron_variant		1	NM_014661.4	P1
FAM53B	ENST00000280780.6	c.134-1009G>A		intron_variant		1
FAM53B	ENST00000392754.7	c.134-1009G>A		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40914 AN: 151990 Hom.: 6388 Cov.: 33

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.269 AC: 40940 AN: 152108 Hom.: 6397 Cov.: 33 AF XY: 0.279 AC XY: 20727 AN XY: 74368

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.281

Alfa AF: 0.284 Hom.: 1090

Bravo AF: 0.254

Asia WGS AF: 0.378 AC: 1314 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	0.16
Dann	Benign	0.45

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: rs4962683; hg19: chr10-126371957;