chr10-124649875-C-T

Variant names:

• chr10-124649875-C-T
• rs7076268
• NM_014661.4:c.907-26271G>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.907-26271G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.933 in 152,232 control chromosomes in the GnomAD database, including 66,986 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 0.93 (66986 hom., cov: 31)
• Consequence: FAM53B NM_014661.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM53B	NM_014661.4	c.907-26271G>A		intron_variant	Intron 4 of 4	ENST00000337318.8	NP_055476.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM53B	ENST00000337318.8	c.907-26271G>A		intron_variant	Intron 4 of 4	1	NM_014661.4	ENSP00000338532.3
ENSG00000258539	ENST00000494792.1	n.*1104-31082G>A		intron_variant	Intron 9 of 9	5		ENSP00000455755.1
FAM53B	ENST00000392754.7	c.907-26271G>A		intron_variant	Intron 4 of 4	2		ENSP00000376509.3

Frequencies

GnomAD3 genomes AF: 0.933 AC: 141867 AN: 152114 Hom.: 66935 Cov.: 31

Gnomad AFR AF: 0.773

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.974

Gnomad ASJ AF: 0.982

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.986

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.940

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

GnomAD4 genome AF: 0.933 AC: 141975 AN: 152232 Hom.: 66986 Cov.: 31 AF XY: 0.936 AC XY: 69679 AN XY: 74436

African (AFR) AF: 0.773 AC: 32055 AN: 41478

American (AMR) AF: 0.974 AC: 14908 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.982 AC: 3411 AN: 3472

East Asian (EAS) AF: 0.985 AC: 5093 AN: 5168

South Asian (SAS) AF: 0.987 AC: 4764 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10622 AN: 10622

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67940 AN: 68036

Other (OTH) AF: 0.941 AC: 1991 AN: 2116

Alfa AF: 0.952 Hom.: 10252

Bravo AF: 0.922

Asia WGS AF: 0.963 AC: 3347 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0020
DANN	Benign	0.58
PhyloP100		-2.0
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: rs7076268; hg19: chr10-126338444;