rs2216460

Positions:

• chr2-224382770-C-A
• chr2-224382770-C-G
• chr2-224382770-C-T

Variant summary

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

The NM_001122779.2(FAM124B):​c.733-2562G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 151,872 control chromosomes in the GnomAD database, including 19,835 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 0.46 (19835 hom., cov: 30)
• Consequence: FAM124B NM_001122779.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129

Genes affected

FAM124B (HGNC:26224): (family with sequence similarity 124 member B) Located in mitochondrion and nucleoplasm. [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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM124B	NM_001122779.2	c.733-2562G>T		intron_variant		ENST00000409685.4	NP_001116251.1
FAM124B	NM_024785.3	c.*39-2562G>T		intron_variant			NP_079061.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM124B	ENST00000409685.4	c.733-2562G>T		intron_variant		2	NM_001122779.2	ENSP00000386895.3
FAM124B	ENST00000389874.3	c.*39-2562G>T		intron_variant		1		ENSP00000374524.3

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70334 AN: 151754 Hom.: 19802 Cov.: 30

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.401

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.464 AC: 70411 AN: 151872 Hom.: 19835 Cov.: 30 AF XY: 0.464 AC XY: 34418 AN XY: 74192

Gnomad4 AFR AF: 0.788

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.726

Gnomad4 SAS AF: 0.369

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.413

Alfa AF: 0.328 Hom.: 4629

Bravo AF: 0.484

Asia WGS AF: 0.538 AC: 1868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.29

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: rs2216460; hg19: chr2-225247487;