chr10-124691769-G-A

Variant names:

• chr10-124691769-G-A
• rs11245330
• NM_014661.4:c.133+4389C>T

Variant summary

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

The NM_014661.4(FAM53B):​c.133+4389C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,200 control chromosomes in the GnomAD database, including 1,547 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 0.13 (1547 hom., cov: 33)
• Consequence: FAM53B NM_014661.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.847
• Publications: 3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM53B	NM_014661.4	c.133+4389C>T		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.133+4389C>T		intron_variant	Intron 3 of 4	1	NM_014661.4	ENSP00000338532.3
FAM53B	ENST00000280780.6	c.133+4389C>T		intron_variant	Intron 3 of 4	1		ENSP00000280780.6
ENSG00000258539	ENST00000494792.1	n.*330+4389C>T		intron_variant	Intron 8 of 9	5		ENSP00000455755.1
FAM53B	ENST00000392754.7	c.133+4389C>T		intron_variant	Intron 3 of 4	2		ENSP00000376509.3

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20247 AN: 152082 Hom.: 1545 Cov.: 33

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.0891

Gnomad FIN AF: 0.0692

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.133 AC: 20259 AN: 152200 Hom.: 1547 Cov.: 33 AF XY: 0.130 AC XY: 9695 AN XY: 74422

African (AFR) AF: 0.185 AC: 7674 AN: 41494

American (AMR) AF: 0.161 AC: 2461 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 400 AN: 3470

East Asian (EAS) AF: 0.142 AC: 735 AN: 5176

South Asian (SAS) AF: 0.0882 AC: 426 AN: 4832

European-Finnish (FIN) AF: 0.0692 AC: 734 AN: 10606

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7445 AN: 68006

Other (OTH) AF: 0.140 AC: 296 AN: 2110

Alfa AF: 0.124 Hom.: 2027

Bravo AF: 0.145

Asia WGS AF: 0.120 AC: 417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.82
PhyloP100		-0.85
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: rs11245330; hg19: chr10-126380338;