NM_001846.4:c.3878-197T>C

Variant names:

• chr13-110502924-T-C
• rs7338575
• NM_001846.4:c.3878-197T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001846.4(COL4A2):​c.3878-197T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 567,166 control chromosomes in the GnomAD database, including 37,926 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (10947 hom., cov: 33)
  • Exomes 𝑓: 0.35 (26979 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.43
• Publications: 4 publications found

Genes affected

COL4A2 (HGNC:2203): (collagen type IV alpha 2 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. The C-terminal portion of the protein, known as canstatin, is an inhibitor of angiogenesis and tumor growth. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. [provided by RefSeq, Jul 2008]

COL4A2-AS1 (HGNC:40156): (COL4A2 antisense RNA 1)

ENSG00000289010 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 13-110502924-T-C is Benign according to our data. Variant chr13-110502924-T-C is described in ClinVar as Benign. ClinVar VariationId is 1235350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001846.4. 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
	COL4A2	NM_001846.4	MANE Select	c.3878-197T>C		intron	N/A	NP_001837.2
	COL4A2-AS1	NR_046583.1		n.191A>G		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	ENST00000360467.7	TSL:5 MANE Select	c.3878-197T>C		intron	N/A	ENSP00000353654.5
	COL4A2-AS1	ENST00000417970.2	TSL:3	n.191A>G		non_coding_transcript_exon	Exon 3 of 3
	COL4A2	ENST00000714399.1		c.3959-197T>C		intron	N/A	ENSP00000519666.1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57138 AN: 152012 Hom.: 10940 Cov.: 33

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.372

GnomAD4 exome AF: 0.354 AC: 147129 AN: 415036 Hom.: 26979 Cov.: 4 AF XY: 0.355 AC XY: 77325 AN XY: 217564

African (AFR) AF: 0.427 AC: 4847 AN: 11346

American (AMR) AF: 0.255 AC: 3599 AN: 14106

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 4497 AN: 12840

East Asian (EAS) AF: 0.172 AC: 4783 AN: 27818

South Asian (SAS) AF: 0.370 AC: 14366 AN: 38870

European-Finnish (FIN) AF: 0.413 AC: 13123 AN: 31790

Middle Eastern (MID) AF: 0.449 AC: 810 AN: 1806

European-Non Finnish (NFE) AF: 0.366 AC: 92348 AN: 252504

Other (OTH) AF: 0.366 AC: 8756 AN: 23956

GnomAD4 genome AF: 0.376 AC: 57176 AN: 152130 Hom.: 10947 Cov.: 33 AF XY: 0.375 AC XY: 27913 AN XY: 74384

African (AFR) AF: 0.431 AC: 17871 AN: 41482

American (AMR) AF: 0.302 AC: 4620 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1188 AN: 3470

East Asian (EAS) AF: 0.200 AC: 1031 AN: 5166

South Asian (SAS) AF: 0.387 AC: 1867 AN: 4828

European-Finnish (FIN) AF: 0.415 AC: 4390 AN: 10580

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.368 AC: 25051 AN: 67992

Other (OTH) AF: 0.370 AC: 780 AN: 2110

Alfa AF: 0.369 Hom.: 3751

Bravo AF: 0.366

Asia WGS AF: 0.297 AC: 1033 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.41
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7338575; hg19: chr13-111155271;