13-110149388-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001845.6(COL4A1):​c.*975A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0032 in 154,772 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 10 hom., cov: 33)
Exomes 𝑓: 0.00042 ( 0 hom. )

Consequence

COL4A1
NM_001845.6 3_prime_UTR

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.141
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 Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 13-110149388-T-G is Benign according to our data. Variant chr13-110149388-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 311006.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAdExome4 highest subpopulation (AMR) allele frequency = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL4A1NM_001845.6 linkc.*975A>C 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.*975A>C 3_prime_UTR_variant Exon 52 of 52 1 NM_001845.6 ENSP00000364979.4 P02462-1
COL4A1ENST00000650424 linkc.*975A>C 3_prime_UTR_variant Exon 10 of 10 ENSP00000497477.2 A0A3B3ISV3
COL4A1ENST00000649720.1 linkn.2153A>C non_coding_transcript_exon_variant Exon 7 of 7

Frequencies

GnomAD3 genomes
AF:
0.00324
AC:
493
AN:
152264
Hom.:
10
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000313
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0126
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0532
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00287
GnomAD4 exome
AF:
0.000418
AC:
1
AN:
2390
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
1218
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.125
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00325
AC:
495
AN:
152382
Hom.:
10
Cov.:
33
AF XY:
0.00378
AC XY:
282
AN XY:
74518
show subpopulations
Gnomad4 AFR
AF:
0.000313
Gnomad4 AMR
AF:
0.0126
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0536
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00331
Alfa
AF:
0.00104
Hom.:
0
Bravo
AF:
0.00502
Asia WGS
AF:
0.0120
AC:
43
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Brain small vessel disease 1 with or without ocular anomalies Benign:2
Jan 12, 2018
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome Benign:1
Jan 12, 2018
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
2.7
DANN
Benign
0.57

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs28362515; hg19: chr13-110801735; API