Genetic Variant ENSG00000258860:n.61+108A>C (chr14-35363460-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000555024.1(ENSG00000258860):n.61+108A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,102 control chromosomes in the GnomAD database, including 27,302 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 ( 27295 hom., cov: 32)

Exomes 𝑓: 0.63 ( 7 hom. )

Consequence

ENSG00000258860
ENST00000555024.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.348

Publications

73 publications found

Variant links:

Genes affected

ENSG00000258860 (HGNC:):

ENSG00000258860 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=-0.92).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000258860	ENST00000555024.1 link	n.61+108A>C		intron_variant	Intron 1 of 1	3
ENSG00000258860	ENST00000723981.1 link	n.*2A>C		downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.597

AC:

90675

AN:

151952

Hom.:

27261

Cov.:

show subpopulations

Gnomad AFR

AF:

0.630

Gnomad AMI

AF:

0.725

Gnomad AMR

AF:

0.693

Gnomad ASJ

AF:

0.558

Gnomad EAS

AF:

0.565

Gnomad SAS

AF:

0.605

Gnomad FIN

AF:

0.570

Gnomad MID

AF:

0.554

Gnomad NFE

AF:

0.562

Gnomad OTH

AF:

0.583

GnomAD4 exome

AF:

0.625

AC:

AN:

Hom.:

AF XY:

0.875

AC XY:

AN XY:

show subpopulations

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

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.650

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000662014), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.367

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.597

AC:

90770

AN:

152070

Hom.:

27295

Cov.:

AF XY:

0.597

AC XY:

44388

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.631

AC:

26150

AN:

41474

American (AMR)

AF:

0.694

AC:

10597

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.558

AC:

1935

AN:

3470

East Asian (EAS)

AF:

0.566

AC:

2922

AN:

5166

South Asian (SAS)

AF:

0.605

AC:

2917

AN:

4822

European-Finnish (FIN)

AF:

0.570

AC:

6030

AN:

10574

Middle Eastern (MID)

AF:

0.544

AC:

160

AN:

294

European-Non Finnish (NFE)

AF:

0.562

AC:

38168

AN:

67968

Other (OTH)

AF:

0.582

AC:

1231

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1882

3764

5647

7529

9411

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

768

1536

2304

3072

3840

<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:

0.570

Hom.:

99692

Bravo

AF:

0.609

Asia WGS

AF:

0.601

AC:

2088

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.78

(source)

DANN

Benign

0.43

PhyloP100

-0.35

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