ENST00000446690.2:n.1008T>A

Variant names:

• chr3-15175196-A-T
• rs11718863
• ENST00000446690.2:n.1008T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.81
• Publications: 21 publications found

Genes affected

COL6A4P1 (HGNC:):

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000446690.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL6A4P1	NR_027927.1		n.1008T>A		non_coding_transcript_exon	Exon 3 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL6A4P1	ENST00000446690.2	TSL:2	n.1008T>A		non_coding_transcript_exon	Exon 3 of 5
	COL6A4P1	ENST00000487147.5	TSL:6	n.832T>A		non_coding_transcript_exon	Exon 3 of 13
	COL6A4P1	ENST00000491915.1	TSL:5	n.-93T>A		upstream_gene	N/A

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

GnomAD2 exomes AF: 0.210 AC: 28809 AN: 136950 AF XY: 0.214

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

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

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

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: 32 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10788 AN: 67982

Other (OTH) AF: 0.168 AC: 354 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	14
DANN	Benign	0.70
PhyloP100		5.8

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11718863;

hg19: chr3-15216703;

COSMIC: COSV71483485;