chr13-110307697-G-C

Variant names:

• chr13-110307697-G-C
• rs7327528
• NM_001846.4:c.-44-163G>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.-44-163G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0627 in 152,176 control chromosomes in the GnomAD database, including 320 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.063 (320 hom., cov: 32)
• Consequence: COL4A2 NM_001846.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.790
• Publications: 2 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, 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=-0.85).
• BP6: Variant 13-110307697-G-C is Benign according to our data. Variant chr13-110307697-G-C is described in ClinVar as Benign. ClinVar VariationId is 1272966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0644 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.-44-163G>C		intron	N/A	NP_001837.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL4A2	ENST00000360467.7	TSL:5 MANE Select	c.-44-163G>C		intron	N/A	ENSP00000353654.5
	COL4A2	ENST00000714399.1		c.-44-163G>C		intron	N/A	ENSP00000519666.1
	COL4A2	ENST00000400163.8	TSL:5	c.-44-163G>C		intron	N/A	ENSP00000383027.4

Frequencies

GnomAD3 genomes AF: 0.0627 AC: 9528 AN: 152058 Hom.: 317 Cov.: 32

Gnomad AFR AF: 0.0636

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.0536

Gnomad ASJ AF: 0.0761

Gnomad EAS AF: 0.0272

Gnomad SAS AF: 0.0552

Gnomad FIN AF: 0.0595

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0660

Gnomad OTH AF: 0.0713

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

GnomAD4 genome AF: 0.0627 AC: 9544 AN: 152176 Hom.: 320 Cov.: 32 AF XY: 0.0629 AC XY: 4681 AN XY: 74414

African (AFR) AF: 0.0639 AC: 2654 AN: 41538

American (AMR) AF: 0.0535 AC: 818 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0761 AC: 264 AN: 3468

East Asian (EAS) AF: 0.0275 AC: 141 AN: 5126

South Asian (SAS) AF: 0.0546 AC: 264 AN: 4832

European-Finnish (FIN) AF: 0.0595 AC: 631 AN: 10610

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0660 AC: 4489 AN: 67986

Other (OTH) AF: 0.0701 AC: 148 AN: 2112

Alfa AF: 0.0650 Hom.: 38

Bravo AF: 0.0617

Asia WGS AF: 0.0480 AC: 168 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	-0.85
CADD	Benign	6.4
DANN	Benign	0.42
PhyloP100		0.79
PromoterAI		0.019	Neutral
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: rs7327528; hg19: chr13-110960044;