10-124655362-C-T

Variant names:

• chr10-124655362-C-T
• rs3781458
• NM_014661.4:c.906+26245G>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.906+26245G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,678 control chromosomes in the GnomAD database, including 23,151 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 0.54 (23151 hom., cov: 30)
• Consequence: FAM53B NM_014661.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177
• Publications: 10 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014661.4. 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
	FAM53B	NM_014661.4	MANE Select	c.906+26245G>A		intron	N/A	NP_055476.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM53B	ENST00000337318.8	TSL:1 MANE Select	c.906+26245G>A		intron	N/A	ENSP00000338532.3
	ENSG00000258539	ENST00000494792.1	TSL:5	n.*1103+26245G>A		intron	N/A	ENSP00000455755.1
	FAM53B	ENST00000392754.7	TSL:2	c.906+26245G>A		intron	N/A	ENSP00000376509.3

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82487 AN: 151558 Hom.: 23135 Cov.: 30

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.544 AC: 82529 AN: 151678 Hom.: 23151 Cov.: 30 AF XY: 0.540 AC XY: 40002 AN XY: 74120

African (AFR) AF: 0.418 AC: 17284 AN: 41340

American (AMR) AF: 0.575 AC: 8765 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1663 AN: 3466

East Asian (EAS) AF: 0.545 AC: 2799 AN: 5138

South Asian (SAS) AF: 0.473 AC: 2265 AN: 4786

European-Finnish (FIN) AF: 0.527 AC: 5559 AN: 10556

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.624 AC: 42310 AN: 67840

Other (OTH) AF: 0.564 AC: 1187 AN: 2106

Alfa AF: 0.586 Hom.: 51467

Bravo AF: 0.543

Asia WGS AF: 0.462 AC: 1612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.2
DANN	Benign	0.54
PhyloP100		0.18
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: rs3781458; hg19: chr10-126343931;