Genetic Variant ENST00000440099.1:n.88+72T>C (chr22-23950077-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000440099.1(ENSG00000231271):n.88+72T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 706 control chromosomes in the GnomAD database, including 54 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 0.60 ( 14837 hom., cov: 39)

Exomes 𝑓: 0.56 ( 54 hom. )

Failed GnomAD Quality Control

Consequence

ENSG00000231271
ENST00000440099.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0420

Publications

17 publications found

Variant links:

Genes affected

ENSG00000231271 (HGNC:):

ENSG00000231271 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.03).

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ENSG00000231271	ENST00000440099.1 link	n.88+72T>C	intron_variant	Intron 1 of 2	6
ENSG00000290199	ENST00000703580.1 link	n.310-23557A>G	intron_variant	Intron 2 of 3
ENSG00000290199	ENST00000717616.1 link	n.136-23557A>G	intron_variant	Intron 1 of 2
ENSG00000290199	ENST00000717617.1 link	n.136-23557A>G	intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.597

AC:

84188

AN:

141026

Hom.:

14798

Cov.:

show subpopulations

Gnomad AFR

AF:

0.714

Gnomad AMI

AF:

0.477

Gnomad AMR

AF:

0.551

Gnomad ASJ

AF:

0.569

Gnomad EAS

AF:

0.638

Gnomad SAS

AF:

0.529

Gnomad FIN

AF:

0.552

Gnomad MID

AF:

0.549

Gnomad NFE

AF:

0.550

Gnomad OTH

AF:

0.578

GnomAD4 exome

AF:

0.561

AC:

396

AN:

706

Hom.:

AF XY:

0.574

AC XY:

233

AN XY:

406

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.917

AC:

AN:

South Asian (SAS)

AF:

0.429

AC:

AN:

European-Finnish (FIN)

AF:

0.570

AC:

357

AN:

626

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.393

AC:

AN:

Other (OTH)

AF:

0.400

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

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

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.597

AC:

84276

AN:

141128

Hom.:

14837

Cov.:

AF XY:

0.594

AC XY:

40935

AN XY:

68924

show subpopulations

African (AFR)

AF:

0.714

AC:

27163

AN:

38030

American (AMR)

AF:

0.551

AC:

7819

AN:

14188

Ashkenazi Jewish (ASJ)

AF:

0.569

AC:

1836

AN:

3228

East Asian (EAS)

AF:

0.639

AC:

2850

AN:

4462

South Asian (SAS)

AF:

0.528

AC:

2271

AN:

4302

European-Finnish (FIN)

AF:

0.552

AC:

5561

AN:

10082

Middle Eastern (MID)

AF:

0.560

AC:

150

AN:

268

European-Non Finnish (NFE)

AF:

0.550

AC:

35109

AN:

63806

Other (OTH)

AF:

0.580

AC:

1128

AN:

1946

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

1489

2978

4466

5955

7444

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

836

1672

2508

3344

4180

<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:

0.412

Hom.:

5380

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

4.1

(source)

DANN

Benign

0.52

PhyloP100

0.042

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