rs2629540

Variant names:

• chr10-124737579-G-C
• rs2629540
• NM_014661.4:c.-175+6434C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 26 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 = 0.245 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.-175+6434C>G		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.-175+6434C>G		intron	N/A	ENSP00000338532.3
	FAM53B	ENST00000280780.6	TSL:1	c.-175+6434C>G		intron	N/A	ENSP00000280780.6
	ENSG00000258539	ENST00000494792.1	TSL:5	n.*23+22807C>G		intron	N/A	ENSP00000455755.1

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

African (AFR) AF: 0.0625 AC: 2596 AN: 41506

American (AMR) AF: 0.156 AC: 2382 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 461 AN: 3466

East Asian (EAS) AF: 0.229 AC: 1184 AN: 5178

South Asian (SAS) AF: 0.137 AC: 659 AN: 4820

European-Finnish (FIN) AF: 0.298 AC: 3152 AN: 10562

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16831 AN: 67960

Other (OTH) AF: 0.189 AC: 398 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.48
PhyloP100		0.046
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: rs2629540; hg19: chr10-126426148;