Genetic Variant ENST00000528221.1:c.432+2T>C (chr8-7296399-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000528221.1(FAM90A20):c.432+2T>C variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 741,910 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 25 hom., cov: 25)

Exomes 𝑓: 0.0012 ( 83 hom. )

Consequence

FAM90A20
ENST00000528221.1 splice_donor, intron

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.653

Publications

0 publications found

Variant links:

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]

FAM90A20 links:

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

FAM66B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BS2

High Homozygotes in GnomAd4 at 25 gene

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
FAM90A20	ENST00000528221.1 link	c.432+2T>C	splice_donor_variant, intron_variant	Intron 3 of 3	6	ENSP00000514265.1	A6NIJ5
FAM66B	ENST00000820789.1 link	n.762+27898A>G	intron_variant	Intron 5 of 5
FAM66B	ENST00000820790.1 link	n.193-2432A>G	intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.00128

AC:

172

AN:

134242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000484

Gnomad ASJ

AF:

0.00117

Gnomad EAS

AF:

0.000612

Gnomad SAS

AF:

0.000881

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00321

Gnomad NFE

AF:

0.00179

Gnomad OTH

AF:

0.00259

GnomAD2 exomes

AF:

0.00131

AC:

304

AN:

232152

AF XY:

0.00115

show subpopulations

Gnomad AFR exome

AF:

0.00184

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.00204

Gnomad EAS exome

AF:

0.00185

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00134

Gnomad OTH exome

AF:

0.00190

GnomAD4 exome

AF:

0.00119

AC:

721

AN:

607604

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

405

AN XY:

331602

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00104

AC:

AN:

12454

American (AMR)

AF:

0.000806

AC:

AN:

42174

Ashkenazi Jewish (ASJ)

AF:

0.00166

AC:

AN:

20514

East Asian (EAS)

AF:

0.00144

AC:

AN:

34608

South Asian (SAS)

AF:

0.00121

AC:

AN:

68588

European-Finnish (FIN)

AF:

0.0000195

AC:

AN:

51276

Middle Eastern (MID)

AF:

0.00370

AC:

AN:

2434

European-Non Finnish (NFE)

AF:

0.00134

AC:

463

AN:

344334

Other (OTH)

AF:

0.00109

AC:

AN:

31222

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.390

Heterozygous variant carriers

103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00129

AC:

173

AN:

134306

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

AN XY:

65734

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00111

AC:

AN:

28006

American (AMR)

AF:

0.000553

AC:

AN:

14470

Ashkenazi Jewish (ASJ)

AF:

0.00117

AC:

AN:

3432

East Asian (EAS)

AF:

0.000614

AC:

AN:

4888

South Asian (SAS)

AF:

0.000882

AC:

AN:

4536

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10330

Middle Eastern (MID)

AF:

0.00345

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00179

AC:

117

AN:

65534

Other (OTH)

AF:

0.00256

AC:

AN:

1954

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.389

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00316

Hom.:

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not provided

Other:1

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

(source)

DANN

Benign

0.50

PhyloP100

0.65

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over