Genetic Variant C20orf96:c.20+6_20+7insTAAAAA (chr20-290584-T-TTTTTTA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_153269.3(C20orf96):c.20+6_20+7insTAAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00318 in 1,546,144 control chromosomes in the GnomAD database, including 65 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.014 ( 32 hom., cov: 0)

Exomes 𝑓: 0.0022 ( 33 hom. )

Consequence

C20orf96
NM_153269.3 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.380

Publications

5 publications found

Variant links:

Genes affected

C20orf96 (HGNC:16227): (chromosome 20 open reading frame 96)

C20orf96 links:

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ACMG classification

Classification was made for transcript

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

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0138 (1860/135250) while in subpopulation AFR AF = 0.0339 (1137/33506). AF 95% confidence interval is 0.0323. There are 32 homozygotes in GnomAd4. There are 860 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C20orf96	NM_153269.3 link	c.20+6_20+7insTAAAAA		splice_region_variant, intron_variant	Intron 1 of 10	ENST00000360321.7	NP_695001.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
C20orf96	ENST00000360321.7 link	c.20+6_20+7insTAAAAA	splice_region_variant, intron_variant	Intron 1 of 10	1	NM_153269.3	ENSP00000353470.2
C20orf96	ENST00000400269.4 link	c.17+2_17+3insTAAAAA	splice_donor_variant, intron_variant	Intron 1 of 10	1		ENSP00000383128.4
C20orf96	ENST00000382369.9 link	c.-245_-244insTAAAAA	upstream_gene_variant		5		ENSP00000371806.5

Frequencies

GnomAD3 genomes

AF:

0.0138

AC:

1861

AN:

135216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0340

Gnomad AMI

AF:

0.0271

Gnomad AMR

AF:

0.00584

Gnomad ASJ

AF:

0.00148

Gnomad EAS

AF:

0.000841

Gnomad SAS

AF:

0.000687

Gnomad FIN

AF:

0.000564

Gnomad MID

AF:

0.00352

Gnomad NFE

AF:

0.00889

Gnomad OTH

AF:

0.0113

GnomAD4 exome

AF:

0.00216

AC:

3051

AN:

1410894

Hom.:

Cov.:

AF XY:

0.00212

AC XY:

1486

AN XY:

701206

show subpopulations

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

African (AFR)

AF:

0.0114

AC:

343

AN:

30064

American (AMR)

AF:

0.00119

AC:

AN:

38628

Ashkenazi Jewish (ASJ)

AF:

0.000636

AC:

AN:

25152

East Asian (EAS)

AF:

0.000310

AC:

AN:

38690

South Asian (SAS)

AF:

0.00138

AC:

112

AN:

81100

European-Finnish (FIN)

AF:

0.00116

AC:

AN:

48470

Middle Eastern (MID)

AF:

0.000970

AC:

AN:

5154

European-Non Finnish (NFE)

AF:

0.00215

AC:

2336

AN:

1085364

Other (OTH)

AF:

0.00215

AC:

125

AN:

58272

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.298

Heterozygous variant carriers

241

482

724

965

1206

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

282

376

470

<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:

0.0138

AC:

1860

AN:

135250

Hom.:

Cov.:

AF XY:

0.0133

AC XY:

860

AN XY:

64896

show subpopulations

African (AFR)

AF:

0.0339

AC:

1137

AN:

33506

American (AMR)

AF:

0.00583

AC:

AN:

13888

Ashkenazi Jewish (ASJ)

AF:

0.00148

AC:

AN:

3378

East Asian (EAS)

AF:

0.000844

AC:

AN:

4740

South Asian (SAS)

AF:

0.000689

AC:

AN:

4354

European-Finnish (FIN)

AF:

0.000564

AC:

AN:

7096

Middle Eastern (MID)

AF:

0.00385

AC:

AN:

260

European-Non Finnish (NFE)

AF:

0.00889

AC:

580

AN:

65268

Other (OTH)

AF:

0.0112

AC:

AN:

1876

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

130

196

261

326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.38

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over