Genetic Variant ENSG00000275431:n.1458G>T (chr17-35987850-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000612584.1(ENSG00000275431):n.1458G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0959 in 152,192 control chromosomes in the GnomAD database, including 770 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 0.096 ( 770 hom., cov: 32)

Exomes 𝑓: 0.071 ( 0 hom. )

Consequence

ENSG00000275431
ENST00000612584.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.143

Publications

12 publications found

Variant links:

Genes affected

ENSG00000275431 (HGNC:):

ENSG00000275431 links:

CCL15-CCL14 (HGNC:44436): (CCL15-CCL14 readthrough (NMD candidate)) A cluster of CC chemokine genes exists on chromosome 17q11.2. The CC chemokines are secreted proteins characterized by two adjacent cysteines. The genes chemokine (C-C motif) ligand 14 and chemokine (C-C motif) ligand 15 are adjacent loci and express read-through transcripts spanning both loci. The read-through transcripts were originally interpreted as bicistronic transcripts, but they are represented as non-coding because they are candidates for nonsense-mediated mRNA decay (NMD). [provided by RefSeq, Dec 2009]

CCL15-CCL14 links:

ENSG00000270240 (HGNC:58767):

ENSG00000270240 links:

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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=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCL15-CCL14	NR_027921.3 link	n.935-1146C>A		intron_variant	Intron 4 of 7
CCL15-CCL14	NR_027922.3 link	n.935-1146C>A		intron_variant	Intron 4 of 6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
ENSG00000275431	ENST00000612584.1 link	n.1458G>T	non_coding_transcript_exon_variant	Exon 2 of 2	1
CCL15-CCL14	ENST00000616694.1 link	n.*47-1146C>A	intron_variant	Intron 4 of 6	2	ENSP00000481402.1
CCL15-CCL14	ENST00000610751.4 link	n.*47-1146C>A	intron_variant	Intron 4 of 7	2	ENSP00000481940.1
ENSG00000270240	ENST00000788510.1 link	n.149-9349G>T	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.0958

AC:

14571

AN:

152060

Hom.:

769

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.0965

Gnomad AMR

AF:

0.0677

Gnomad ASJ

AF:

0.0766

Gnomad EAS

AF:

0.0931

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.150

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0874

Gnomad OTH

AF:

0.0837

GnomAD4 exome

AF:

0.0714

AC:

AN:

Hom.:

Cov.:

AF XY:

0.100

AC XY:

AN XY:

show subpopulations

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:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.100

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0959

AC:

14596

AN:

152178

Hom.:

770

Cov.:

AF XY:

0.0996

AC XY:

7406

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.107

AC:

4422

AN:

41510

American (AMR)

AF:

0.0676

AC:

1034

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0766

AC:

266

AN:

3472

East Asian (EAS)

AF:

0.0924

AC:

479

AN:

5184

South Asian (SAS)

AF:

0.117

AC:

566

AN:

4824

European-Finnish (FIN)

AF:

0.150

AC:

1587

AN:

10566

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0874

AC:

5945

AN:

68008

Other (OTH)

AF:

0.0848

AC:

179

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

675

1350

2026

2701

3376

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

336

504

672

840

<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:

0.0855

Hom.:

1673

Bravo

AF:

0.0893

Asia WGS

AF:

0.152

AC:

527

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.80

(source)

DANN

Benign

0.30

PhyloP100

-0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over