8-7296399-T-G

Variant names:

• chr8-7296399-T-G
• rs201746613
• ENST00000528221.1:c.432+2T>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000528221.1(FAM90A20):​c.432+2T>G variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000987 in 608,028 control chromosomes in the GnomAD database, including 2 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: not found (cov: 25)
  • Exomes 𝑓: 0.0000099 (2 hom.)
• Consequence: FAM90A20 ENST00000528221.1 splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.653
• Publications: 0 publications found

Genes affected

FAM90A20 (HGNC:32268): (family with sequence similarity 90 member A20) FAM90A20 belongs to subfamily II of the primate-specific FAM90A gene family, which originated from multiple duplications and rearrangements (Bosch et al., 2007 [PubMed 17684299]). For background information on the FAM90A gene family, as well as information on the evolution of FAM90A genes, see FAM90A1 (MIM 613041).[supplied by OMIM, Oct 2009]

FAM66B (HGNC:28890): (family with sequence similarity 66 member B)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS2: High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM90A20	NM_001423532.1	c.432+2T>G		splice_donor_variant, intron_variant	Intron 3 of 3		NP_001410461.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM90A20	ENST00000528221.1	c.432+2T>G		splice_donor_variant, intron_variant	Intron 3 of 3	6		ENSP00000514265.1
FAM66B	ENST00000820789.1	n.762+27898A>C		intron_variant	Intron 5 of 5
FAM66B	ENST00000820790.1	n.193-2432A>C		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD2 exomes AF: 0.0000215 AC: 5 AN: 232152 AF XY: 0.0000158

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000472

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000987 AC: 6 AN: 608028 Hom.: 2 Cov.: 6 AF XY: 0.0000121 AC XY: 4 AN XY: 331822

African (AFR) AF: 0.00 AC: 0 AN: 12454

American (AMR) AF: 0.00 AC: 0 AN: 42186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20520

East Asian (EAS) AF: 0.00 AC: 0 AN: 34620

South Asian (SAS) AF: 0.00 AC: 0 AN: 68614

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2434

European-Non Finnish (NFE) AF: 0.0000174 AC: 6 AN: 344678

Other (OTH) AF: 0.00 AC: 0 AN: 31244

GnomAD4 genome Cov.: 25

Alfa AF: 0.00 Hom.: 16

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	17
DANN	Benign	0.50
PhyloP100		0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs201746613; hg19: chr8-7153921;