6-56242467-A-T

Variant names:

• chr6-56242467-A-T
• rs1925156
• NM_030820.4:c.-39+4920T>A

Variant summary

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

The NM_030820.4(COL21A1):​c.-39+4920T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 151,968 control chromosomes in the GnomAD database, including 17,760 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 0.46 (17760 hom., cov: 32)
• Consequence: COL21A1 NM_030820.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23
• Publications: 4 publications found

Genes affected

COL21A1 (HGNC:17025): (collagen type XXI alpha 1 chain) This gene encodes the alpha chain of type XXI collagen, a member of the FACIT (fibril-associated collagens with interrupted helices) collagen family. Type XXI collagen is localized to tissues containing type I collagen and maintains the integrity of the extracellular matrix. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030820.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL21A1	NM_030820.4	MANE Select	c.-39+4920T>A		intron	N/A	NP_110447.2
	COL21A1	NM_001318751.2		c.-113+4920T>A		intron	N/A	NP_001305680.1
	COL21A1	NM_001318752.2		c.-38-59811T>A		intron	N/A	NP_001305681.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL21A1	ENST00000244728.10	TSL:1 MANE Select	c.-39+4920T>A		intron	N/A	ENSP00000244728.5
	COL21A1	ENST00000370819.5	TSL:1	c.-38-59811T>A		intron	N/A	ENSP00000359855.1
	COL21A1	ENST00000370817.3	TSL:3	c.-165+4920T>A		intron	N/A	ENSP00000359853.3

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70171 AN: 151850 Hom.: 17743 Cov.: 32

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.0956

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.426

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.399

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.462 AC: 70221 AN: 151968 Hom.: 17760 Cov.: 32 AF XY: 0.457 AC XY: 33941 AN XY: 74276

African (AFR) AF: 0.654 AC: 27085 AN: 41442

American (AMR) AF: 0.363 AC: 5546 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1415 AN: 3460

East Asian (EAS) AF: 0.0953 AC: 492 AN: 5164

South Asian (SAS) AF: 0.298 AC: 1436 AN: 4820

European-Finnish (FIN) AF: 0.453 AC: 4782 AN: 10556

Middle Eastern (MID) AF: 0.424 AC: 122 AN: 288

European-Non Finnish (NFE) AF: 0.418 AC: 28390 AN: 67944

Other (OTH) AF: 0.395 AC: 832 AN: 2106

Alfa AF: 0.299 Hom.: 673

Bravo AF: 0.459

Asia WGS AF: 0.225 AC: 787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.78
PhyloP100		2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1925156; hg19: chr6-56107265;