Genetic Variant ENST00000446690.2:n.1008T>A (chr3-15175196-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000446690.2(COL6A4P1):n.1008T>A variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.184 in 459,080 control chromosomes in the GnomAD database, including 9,516 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 0.16 ( 2405 hom., cov: 32)

Exomes 𝑓: 0.20 ( 7111 hom. )

Consequence

COL6A4P1
ENST00000446690.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.81

Publications

21 publications found

Variant links:

COSMIC-nc: COSV71483485

Genes affected

COL6A4P1 (HGNC:):

COL6A4P1 links:

COL6A4P1 (HGNC:33484): (collagen type VI alpha 4 pseudogene 1) This transcribed pseudogene represents the 5' end of a presumed ortholog to a mouse gene which encodes a collagen VI alpha 4 chain protein (GeneID 68553). No complete ORF of comparable size to the mouse protein is found in this gene. The predicted protein lacks a signal peptide; however, this truncated collagen polypeptide may have achieved a different function as suggested by PubMed ID: 18622395. Evidence of in vivo translation is incomplete. A large chromosome break separates this pseudogene from the 3' end of the presumed ortholog (COL6A4P2, GeneID 646300) which is located downstream at chromosome 3q21.3. [provided by RefSeq, Jun 2009]

COL6A4P1 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=-0.48).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL6A4P1	NR_027927.1 link	n.1008T>A		non_coding_transcript_exon_variant	Exon 3 of 5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
COL6A4P1	ENST00000446690.2 link	n.1008T>A	non_coding_transcript_exon_variant	Exon 3 of 5	2
COL6A4P1	ENST00000487147.5 link	n.832T>A	non_coding_transcript_exon_variant	Exon 3 of 13	6
COL6A4P1	ENST00000491915.1 link	n.-93T>A	upstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.158

AC:

24068

AN:

152002

Hom.:

2394

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0987

Gnomad AMI

AF:

0.169

Gnomad AMR

AF:

0.194

Gnomad ASJ

AF:

0.0836

Gnomad EAS

AF:

0.490

Gnomad SAS

AF:

0.315

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.159

GnomAD2 exomes

AF:

0.210

AC:

28809

AN:

136950

AF XY:

0.214

show subpopulations

Gnomad AFR exome

AF:

0.0941

Gnomad AMR exome

AF:

0.225

Gnomad ASJ exome

AF:

0.0766

Gnomad EAS exome

AF:

0.497

Gnomad FIN exome

AF:

0.138

Gnomad NFE exome

AF:

0.158

Gnomad OTH exome

AF:

0.170

GnomAD4 exome

AF:

0.196

AC:

60220

AN:

306960

Hom.:

7111

Cov.:

AF XY:

0.206

AC XY:

36001

AN XY:

174728

show subpopulations

African (AFR)

AF:

0.0953

AC:

830

AN:

8708

American (AMR)

AF:

0.225

AC:

6137

AN:

27332

Ashkenazi Jewish (ASJ)

AF:

0.0783

AC:

851

AN:

10866

East Asian (EAS)

AF:

0.485

AC:

4638

AN:

9566

South Asian (SAS)

AF:

0.292

AC:

17449

AN:

59754

European-Finnish (FIN)

AF:

0.139

AC:

1832

AN:

13164

Middle Eastern (MID)

AF:

0.119

AC:

334

AN:

2796

European-Non Finnish (NFE)

AF:

0.159

AC:

25523

AN:

160426

Other (OTH)

AF:

0.183

AC:

2626

AN:

14348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

3308

6616

9925

13233

16541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

284

568

852

1136

1420

<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:

0.158

AC:

24104

AN:

152120

Hom.:

2405

Cov.:

AF XY:

0.163

AC XY:

12142

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0987

AC:

4096

AN:

41520

American (AMR)

AF:

0.194

AC:

2968

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.0836

AC:

290

AN:

3470

East Asian (EAS)

AF:

0.490

AC:

2533

AN:

5172

South Asian (SAS)

AF:

0.317

AC:

1522

AN:

4808

European-Finnish (FIN)

AF:

0.129

AC:

1367

AN:

10586

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.159

AC:

10788

AN:

67982

Other (OTH)

AF:

0.168

AC:

354

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

999

1997

2996

3994

4993

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

280

560

840

1120

1400

<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:

0.0974

Hom.:

205

Bravo

AF:

0.159

Asia WGS

AF:

0.393

AC:

1366

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.70

PhyloP100

5.8

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

Computational scores

Splicing

Publications

Other links and lift over