chr10-124713227-A-G

Variant names:

• chr10-124713227-A-G
• rs4962399
• NM_014661.4:c.-174-6340T>C

Variant summary

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

The NM_014661.4(FAM53B):​c.-174-6340T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,216 control chromosomes in the GnomAD database, including 1,121 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 0.11 (1121 hom., cov: 33)
• Consequence: FAM53B NM_014661.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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]

FAM53B-AS1 (HGNC:49499): (FAM53B antisense RNA 1)

ENSG00000258539 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM53B	NM_014661.4	c.-174-6340T>C		intron_variant	Intron 1 of 4	ENST00000337318.8	NP_055476.3
FAM53B-AS1	NR_120630.1	n.445-207A>G		intron_variant	Intron 2 of 2
FAM53B-AS1	NR_120631.1	n.305-207A>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM53B	ENST00000337318.8	c.-174-6340T>C		intron_variant	Intron 1 of 4	1	NM_014661.4	ENSP00000338532.3
ENSG00000258539	ENST00000494792.1	n.*24-6340T>C		intron_variant	Intron 6 of 9	5		ENSP00000455755.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17314 AN: 152098 Hom.: 1120 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.0632

Gnomad FIN AF: 0.0654

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.114 AC: 17327 AN: 152216 Hom.: 1121 Cov.: 33 AF XY: 0.112 AC XY: 8303 AN XY: 74420

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.0624

Gnomad4 FIN AF: 0.0654

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.123

Alfa AF: 0.118 Hom.: 180

Bravo AF: 0.124

Asia WGS AF: 0.107 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.5
DANN	Benign	0.78

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: rs4962399; hg19: chr10-126401796;