rs4962683

Variant names:

• chr10-124683388-C-T
• rs4962683
• NM_014661.4:c.134-1009G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

ENSG00000258539 (HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM53B	NM_014661.4	c.134-1009G>A		intron_variant	Intron 3 of 4	ENST00000337318.8	NP_055476.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM53B	ENST00000337318.8	c.134-1009G>A		intron_variant	Intron 3 of 4	1	NM_014661.4	ENSP00000338532.3
FAM53B	ENST00000280780.6	c.134-1009G>A		intron_variant	Intron 3 of 4	1		ENSP00000280780.6
ENSG00000258539	ENST00000494792.1	n.*331-1009G>A		intron_variant	Intron 8 of 9	5		ENSP00000455755.1
FAM53B	ENST00000392754.7	c.134-1009G>A		intron_variant	Intron 3 of 4	2		ENSP00000376509.3

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

African (AFR) AF: 0.118 AC: 4885 AN: 41478

American (AMR) AF: 0.317 AC: 4840 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1532 AN: 3470

East Asian (EAS) AF: 0.318 AC: 1645 AN: 5174

South Asian (SAS) AF: 0.384 AC: 1854 AN: 4824

European-Finnish (FIN) AF: 0.433 AC: 4577 AN: 10566

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20681 AN: 67992

Other (OTH) AF: 0.281 AC: 594 AN: 2112

Alfa AF: 0.285 Hom.: 2172

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
PhyloP100		-1.6
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: rs4962683; hg19: chr10-126371957;