rs9303621

chr17-28834120-A-Gchr17-28834120-A-T

Variant summary

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

The NM_001077498.3(FAM222B):c.-41+8562T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,084 control chromosomes in the GnomAD database, including 2,970 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 (2970 hom., cov: 31)
• Consequence: FAM222B NM_001077498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.328

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM222B	NM_001077498.3	c.-41+8562T>C		intron_variant		ENST00000581407.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM222B	ENST00000581407.6	c.-41+8562T>C		intron_variant		1	NM_001077498.3	P1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29423 AN: 151966 Hom.: 2964 Cov.: 31

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.194 AC: 29446 AN: 152084 Hom.: 2970 Cov.: 31 AF XY: 0.194 AC XY: 14409 AN XY: 74346

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.194

Alfa AF: 0.202 Hom.: 1647

Bravo AF: 0.193

Asia WGS AF: 0.245 AC: 855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	7.3
Dann	Benign	0.64

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: rs9303621; hg19: chr17-27161138;