17-28768467-G-A

Variant names:

• chr17-28768467-G-A
• rs11658900
• NM_001077498.3:c.-40-1760C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001077498.3(FAM222B):​c.-40-1760C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 151,790 control chromosomes in the GnomAD database, including 16,329 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 0.42 (16329 hom., cov: 30)
• Consequence: FAM222B NM_001077498.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.353
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077498.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM222B	NM_001077498.3	MANE Select	c.-40-1760C>T		intron	N/A	NP_001070966.1
	FAM222B	NM_001288631.2		c.-205-1760C>T		intron	N/A	NP_001275560.1
	FAM222B	NM_001288632.2		c.-40-1760C>T		intron	N/A	NP_001275561.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM222B	ENST00000581407.6	TSL:1 MANE Select	c.-40-1760C>T		intron	N/A	ENSP00000462419.1
	FAM222B	ENST00000582266.6	TSL:1	c.-40-1760C>T		intron	N/A	ENSP00000462534.1
	FAM222B	ENST00000452648.8	TSL:2	c.-40-1760C>T		intron	N/A	ENSP00000413645.3

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63751 AN: 151672 Hom.: 16325 Cov.: 30

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.420 AC: 63754 AN: 151790 Hom.: 16329 Cov.: 30 AF XY: 0.422 AC XY: 31281 AN XY: 74190

African (AFR) AF: 0.111 AC: 4591 AN: 41436

American (AMR) AF: 0.442 AC: 6738 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1980 AN: 3472

East Asian (EAS) AF: 0.587 AC: 3022 AN: 5150

South Asian (SAS) AF: 0.510 AC: 2447 AN: 4794

European-Finnish (FIN) AF: 0.526 AC: 5543 AN: 10530

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.559 AC: 37930 AN: 67876

Other (OTH) AF: 0.456 AC: 959 AN: 2102

Alfa AF: 0.512 Hom.: 36878

Bravo AF: 0.404

Asia WGS AF: 0.533 AC: 1852 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.96
DANN	Benign	0.30
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11658900; hg19: chr17-27095485;