chr10-124650088-A-G

Variant names:

• chr10-124650088-A-G
• rs10736889
• NM_014661.4:c.907-26484T>C

Variant summary

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

The NM_014661.4(FAM53B):​c.907-26484T>C 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 152,054 control chromosomes in the GnomAD database, including 23,193 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 (23193 hom., cov: 32)
• Consequence: FAM53B NM_014661.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.30
• Publications: 6 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=-0.62).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM53B	NM_014661.4	MANE Select	c.907-26484T>C		intron	N/A	NP_055476.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM53B	ENST00000337318.8	TSL:1 MANE Select	c.907-26484T>C		intron	N/A	ENSP00000338532.3
	ENSG00000258539	ENST00000494792.1	TSL:5	n.*1104-31295T>C		intron	N/A	ENSP00000455755.1
	FAM53B	ENST00000392754.7	TSL:2	c.907-26484T>C		intron	N/A	ENSP00000376509.3

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82638 AN: 151936 Hom.: 23177 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.544 AC: 82684 AN: 152054 Hom.: 23193 Cov.: 32 AF XY: 0.539 AC XY: 40104 AN XY: 74346

African (AFR) AF: 0.416 AC: 17240 AN: 41458

American (AMR) AF: 0.574 AC: 8767 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1667 AN: 3472

East Asian (EAS) AF: 0.544 AC: 2811 AN: 5164

South Asian (SAS) AF: 0.476 AC: 2291 AN: 4816

European-Finnish (FIN) AF: 0.527 AC: 5565 AN: 10560

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

European-Non Finnish (NFE) AF: 0.624 AC: 42451 AN: 67982

Other (OTH) AF: 0.563 AC: 1191 AN: 2114

Alfa AF: 0.585 Hom.: 4450

Bravo AF: 0.542

Asia WGS AF: 0.463 AC: 1613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	11
DANN	Benign	0.48
PhyloP100		3.3
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: rs10736889; hg19: chr10-126338657;