rs41315048

Variant names:

• chr13-110485628-G-T
• rs41315048
• NM_001846.4:c.3026-27G>T

Your query was ambiguous. Multiple possible variants found:

• chr13-110485628-G-T
• chr13-110485628-G-A

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.3026-27G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0562 in 1,569,564 control chromosomes in the GnomAD database, including 2,694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (231 hom., cov: 32)
  • Exomes 𝑓: 0.057 (2463 hom.)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.273
• 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 Gene-Disease associations (from GenCC):

• porencephaly 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• COL4A1 or COL4A2-related cerebral small vessel disease

  Inheritance: AD Classification: MODERATE Submitted by: Illumina
• familial porencephaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 13-110485628-G-T is Benign according to our data. Variant chr13-110485628-G-T is described in ClinVar as Benign. ClinVar VariationId is 1228626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0614 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	NM_001846.4	MANE Select	c.3026-27G>T		intron	N/A	NP_001837.2	P08572

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	ENST00000360467.7	TSL:5 MANE Select	c.3026-27G>T		intron	N/A	ENSP00000353654.5	P08572
	COL4A2	ENST00000714399.1		c.3107-27G>T		intron	N/A	ENSP00000519666.1	A0AAQ5BHW7
	COL4A2	ENST00000400163.8	TSL:5	c.3026-27G>T		intron	N/A	ENSP00000383027.4	P08572

Frequencies

GnomAD3 genomes AF: 0.0518 AC: 7880 AN: 151988 Hom.: 231 Cov.: 32

Gnomad AFR AF: 0.0321

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.0649

Gnomad ASJ AF: 0.0522

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0470

Gnomad FIN AF: 0.0688

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.0627

Gnomad OTH AF: 0.0488

GnomAD2 exomes AF: 0.0528 AC: 11642 AN: 220630 AF XY: 0.0538

Gnomad AFR exome AF: 0.0306

Gnomad AMR exome AF: 0.0608

Gnomad ASJ exome AF: 0.0523

Gnomad EAS exome AF: 0.000184

Gnomad FIN exome AF: 0.0751

Gnomad NFE exome AF: 0.0594

Gnomad OTH exome AF: 0.0672

GnomAD4 exome AF: 0.0567 AC: 80379 AN: 1417464 Hom.: 2463 Cov.: 30 AF XY: 0.0568 AC XY: 39923 AN XY: 702460

African (AFR) AF: 0.0337 AC: 1049 AN: 31158

American (AMR) AF: 0.0625 AC: 2172 AN: 34744

Ashkenazi Jewish (ASJ) AF: 0.0574 AC: 1380 AN: 24052

East Asian (EAS) AF: 0.0000512 AC: 2 AN: 39090

South Asian (SAS) AF: 0.0452 AC: 3699 AN: 81788

European-Finnish (FIN) AF: 0.0720 AC: 3768 AN: 52332

Middle Eastern (MID) AF: 0.0770 AC: 429 AN: 5570

European-Non Finnish (NFE) AF: 0.0592 AC: 64534 AN: 1090370

Other (OTH) AF: 0.0573 AC: 3346 AN: 58360

GnomAD4 genome AF: 0.0519 AC: 7890 AN: 152100 Hom.: 231 Cov.: 32 AF XY: 0.0513 AC XY: 3817 AN XY: 74354

African (AFR) AF: 0.0323 AC: 1341 AN: 41514

American (AMR) AF: 0.0648 AC: 990 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0522 AC: 181 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5174

South Asian (SAS) AF: 0.0473 AC: 228 AN: 4818

European-Finnish (FIN) AF: 0.0688 AC: 726 AN: 10554

Middle Eastern (MID) AF: 0.107 AC: 31 AN: 290

European-Non Finnish (NFE) AF: 0.0627 AC: 4260 AN: 67976

Other (OTH) AF: 0.0487 AC: 103 AN: 2114

Alfa AF: 0.0601 Hom.: 98

Bravo AF: 0.0496

Asia WGS AF: 0.0270 AC: 93 AN: 3478

ClinVar

ClinVar submissions

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	-0.83
CADD	Benign	0.41
DANN	Benign	0.59
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs41315048; hg19: chr13-111137975;