3-15175196-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_027927.1(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 NR_027927.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.81

Genes affected

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
COL6A4P1	NR_027927.1	n.1008T>A		non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL6A4P1	ENST00000446690.2	n.1008T>A		non_coding_transcript_exon_variant	3/5	2
COL6A4P1	ENST00000487147.5	n.832T>A		non_coding_transcript_exon_variant	3/13

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24068 AN: 152002 Hom.: 2394 Cov.: 32

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

GnomAD3 exomes AF: 0.210 AC: 28809 AN: 136950 Hom.: 3836 AF XY: 0.214 AC XY: 15898 AN XY: 74360

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 SAS exome AF: 0.297

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.: 0 AF XY: 0.206 AC XY: 36001 AN XY: 174728

Gnomad4 AFR exome AF: 0.0953

Gnomad4 AMR exome AF: 0.225

Gnomad4 ASJ exome AF: 0.0783

Gnomad4 EAS exome AF: 0.485

Gnomad4 SAS exome AF: 0.292

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.159

Gnomad4 OTH exome AF: 0.183

GnomAD4 genome AF: 0.158 AC: 24104 AN: 152120 Hom.: 2405 Cov.: 32 AF XY: 0.163 AC XY: 12142 AN XY: 74344

Gnomad4 AFR AF: 0.0987

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.0836

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.168

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	14
Dann	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11718863; hg19: chr3-15216703; COSMIC: COSV71483485;