17-28760911-C-T

Variant names:

• chr17-28760911-C-T
• rs4795457
• NM_001077498.3:c.83-1035G>A

Variant summary

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

The NM_001077498.3(FAM222B):​c.83-1035G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,144 control chromosomes in the GnomAD database, including 2,876 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 (2876 hom., cov: 32)
• Consequence: FAM222B NM_001077498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.247

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=-0.68).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM222B	NM_001077498.3	c.83-1035G>A		intron_variant	Intron 2 of 2	ENST00000581407.6	NP_001070966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM222B	ENST00000581407.6	c.83-1035G>A		intron_variant	Intron 2 of 2	1	NM_001077498.3	ENSP00000462419.1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28819 AN: 152026 Hom.: 2870 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.190 AC: 28834 AN: 152144 Hom.: 2876 Cov.: 32 AF XY: 0.190 AC XY: 14146 AN XY: 74380

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.193

Alfa AF: 0.202 Hom.: 1918

Bravo AF: 0.188

Asia WGS AF: 0.247 AC: 860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.8
DANN	Benign	0.61

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: rs4795457; hg19: chr17-27087929;