rs2629540

Positions:

• chr10-124737579-G-C

Variant summary

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

The NM_014661.4(FAM53B):​c.-175+6434C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,096 control chromosomes in the GnomAD database, including 3,239 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 0.19 (3239 hom., cov: 32)
• Consequence: FAM53B NM_014661.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM53B	NM_014661.4	c.-175+6434C>G		intron_variant		ENST00000337318.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM53B	ENST00000337318.8	c.-175+6434C>G		intron_variant		1	NM_014661.4	P1
FAM53B	ENST00000280780.6	c.-175+6434C>G		intron_variant		1
FAM53B	ENST00000392754.7	c.-175+4849C>G		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28205 AN: 151976 Hom.: 3236 Cov.: 32

Gnomad AFR AF: 0.0626

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.185 AC: 28203 AN: 152096 Hom.: 3239 Cov.: 32 AF XY: 0.187 AC XY: 13930 AN XY: 74336

Gnomad4 AFR AF: 0.0625

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.189

Alfa AF: 0.204 Hom.: 447

Bravo AF: 0.172

Asia WGS AF: 0.151 AC: 531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.48

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: rs2629540; hg19: chr10-126426148;