rs2043031

Positions:

• chr17-28758546-A-G
• chr17-28758546-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001077498.3(FAM222B):​c.1413T>C​(p.Leu471Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,610,036 control chromosomes in the GnomAD database, including 35,829 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 (2883 hom., cov: 32)
  • Exomes 𝑓: 0.21 (32946 hom.)
• Consequence: FAM222B NM_001077498.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370

Genes affected

FAM222B (HGNC:25563): (family with sequence similarity 222 member B) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-0.37 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM222B	NM_001077498.3	c.1413T>C	p.Leu471Leu	synonymous_variant	3/3	ENST00000581407.6	NP_001070966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM222B	ENST00000581407.6	c.1413T>C	p.Leu471Leu	synonymous_variant	3/3	1	NM_001077498.3	ENSP00000462419.1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28869 AN: 152052 Hom.: 2878 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.192

GnomAD3 exomes AF: 0.211 AC: 51640 AN: 244498 Hom.: 5704 AF XY: 0.214 AC XY: 28508 AN XY: 133090

Gnomad AFR exome AF: 0.150

Gnomad AMR exome AF: 0.208

Gnomad ASJ exome AF: 0.242

Gnomad EAS exome AF: 0.190

Gnomad SAS exome AF: 0.320

Gnomad FIN exome AF: 0.191

Gnomad NFE exome AF: 0.194

Gnomad OTH exome AF: 0.218

GnomAD4 exome AF: 0.209 AC: 304464 AN: 1457868 Hom.: 32946 Cov.: 35 AF XY: 0.212 AC XY: 153782 AN XY: 725420

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.212

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.251

Gnomad4 SAS exome AF: 0.312

Gnomad4 FIN exome AF: 0.186

Gnomad4 NFE exome AF: 0.201

Gnomad4 OTH exome AF: 0.206

GnomAD4 genome AF: 0.190 AC: 28882 AN: 152168 Hom.: 2883 Cov.: 32 AF XY: 0.190 AC XY: 14164 AN XY: 74384

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.193

Alfa AF: 0.199 Hom.: 4552

Bravo AF: 0.189

Asia WGS AF: 0.250 AC: 870 AN: 3478

EpiCase AF: 0.196

EpiControl AF: 0.191

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.57

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: rs2043031; hg19: chr17-27085564; COSMIC: COSV57930323; COSMIC: COSV57930323;