13-110149715-A-AAT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001845.6(COL4A1):​c.*646_*647dupAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000508 in 151,694 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0023 ( 0 hom. )

Consequence

COL4A1
NM_001845.6 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:3

Conservation

PhyloP100: 3.41
Variant links:
Genes affected
COL4A1 (HGNC:2202): (collagen type IV alpha 1 chain) This gene encodes a type IV collagen alpha protein. Type IV collagen proteins are integral components of basement membranes. This gene shares a bidirectional promoter with a paralogous gene on the opposite strand. The protein consists of an amino-terminal 7S domain, a triple-helix forming collagenous domain, and a carboxy-terminal non-collagenous domain. It functions as part of a heterotrimer and interacts with other extracellular matrix components such as perlecans, proteoglycans, and laminins. In addition, proteolytic cleavage of the non-collagenous carboxy-terminal domain results in a biologically active fragment known as arresten, which has anti-angiogenic and tumor suppressor properties. Mutations in this gene cause porencephaly, cerebrovascular disease, and renal and muscular defects. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd4 at 76 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL4A1NM_001845.6 linkc.*646_*647dupAT 3_prime_UTR_variant Exon 52 of 52 ENST00000375820.10 NP_001836.3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL4A1ENST00000375820 linkc.*646_*647dupAT 3_prime_UTR_variant Exon 52 of 52 1 NM_001845.6 ENSP00000364979.4 P02462-1
COL4A1ENST00000650424 linkc.*646_*647dupAT 3_prime_UTR_variant Exon 10 of 10 ENSP00000497477.2 A0A3B3ISV3
COL4A1ENST00000649720.1 linkn.1824_1825dupAT non_coding_transcript_exon_variant Exon 7 of 7

Frequencies

GnomAD3 genomes
AF:
0.000503
AC:
76
AN:
151150
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000485
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000264
Gnomad ASJ
AF:
0.000289
Gnomad EAS
AF:
0.00116
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00550
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00228
AC:
1
AN:
438
Hom.:
0
Cov.:
0
AF XY:
0.00373
AC XY:
1
AN XY:
268
show subpopulations
Gnomad4 FIN exome
AF:
0.00239
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000502
AC:
76
AN:
151256
Hom.:
0
Cov.:
33
AF XY:
0.000785
AC XY:
58
AN XY:
73894
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.000263
Gnomad4 ASJ
AF:
0.000289
Gnomad4 EAS
AF:
0.00116
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00550
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000185

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:3
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Brain small vessel disease 1 with or without ocular anomalies Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Porencephalic cyst Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs886049952; hg19: chr13-110802062; API