Genetic Variant COL6A4P1: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:

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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=-0.48).

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

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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