Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_033641.4(COL4A6):c.3078C>T(p.Gly1026Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,208,104 control chromosomes in the GnomAD database, including 30,479 homozygotes. There are 99,687 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 3298 hom., 8661 hem., cov: 22)

Exomes 𝑓: 0.25 ( 27181 hom. 91026 hem. )

Consequence

COL4A6
NM_033641.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.250

Publications

19 publications found

Variant links:

Genes affected

COL4A6 (HGNC:2208): (collagen type IV alpha 6 chain) This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. 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, alpha 5 type IV collagen, so that the gene pair shares a common promoter. Deletions in the alpha 5 gene that extend into the alpha 6 gene result in diffuse leiomyomatosis accompanying the X-linked Alport syndrome caused by the deletion in the alpha 5 gene. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2013]

COL4A6 Gene-Disease associations (from GenCC):

hearing loss, X-linked 6
Inheritance: XL Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, PanelApp Australia
X-linked nonsyndromic hearing loss
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
premature ovarian failure 1
Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

COL4A6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant X-108174500-G-A is Benign according to our data. Variant chrX-108174500-G-A is described in ClinVar as Benign. ClinVar VariationId is 258271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.25 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033641.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
COL4A6	NM_033641.4	MANE Select	c.3078C>T	p.Gly1026Gly	synonymous	Exon 31 of 45	NP_378667.1
COL4A6	NM_001287758.2		c.3129C>T	p.Gly1043Gly	synonymous	Exon 32 of 46	NP_001274687.1
COL4A6	NM_001847.4		c.3081C>T	p.Gly1027Gly	synonymous	Exon 31 of 45	NP_001838.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
COL4A6	ENST00000334504.12	TSL:5 MANE Select	c.3078C>T	p.Gly1026Gly	synonymous	Exon 31 of 45	ENSP00000334733.7
COL4A6	ENST00000372216.8	TSL:1	c.3081C>T	p.Gly1027Gly	synonymous	Exon 31 of 45	ENSP00000361290.4
COL4A6	ENST00000621266.4	TSL:1	c.3078C>T	p.Gly1026Gly	synonymous	Exon 31 of 44	ENSP00000482970.1

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

29575

AN:

110542

Hom.:

3293

Cov.:

show subpopulations

Gnomad AFR

AF:

0.277

Gnomad AMI

AF:

0.220

Gnomad AMR

AF:

0.476

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.613

Gnomad SAS

AF:

0.372

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.214

Gnomad NFE

AF:

0.213

Gnomad OTH

AF:

0.267

GnomAD2 exomes

AF:

0.319

AC:

58149

AN:

182244

AF XY:

0.303

show subpopulations

Gnomad AFR exome

AF:

0.282

Gnomad AMR exome

AF:

0.623

Gnomad ASJ exome

AF:

0.190

Gnomad EAS exome

AF:

0.606

Gnomad FIN exome

AF:

0.147

Gnomad NFE exome

AF:

0.208

Gnomad OTH exome

AF:

0.278

GnomAD4 exome

AF:

0.249

AC:

273774

AN:

1097504

Hom.:

27181

Cov.:

AF XY:

0.251

AC XY:

91026

AN XY:

363012

show subpopulations

African (AFR)

AF:

0.289

AC:

7619

AN:

26378

American (AMR)

AF:

0.603

AC:

21177

AN:

35141

Ashkenazi Jewish (ASJ)

AF:

0.188

AC:

3631

AN:

19362

East Asian (EAS)

AF:

0.669

AC:

20188

AN:

30169

South Asian (SAS)

AF:

0.379

AC:

20507

AN:

54070

European-Finnish (FIN)

AF:

0.154

AC:

6245

AN:

40510

Middle Eastern (MID)

AF:

0.206

AC:

852

AN:

4129

European-Non Finnish (NFE)

AF:

0.216

AC:

181505

AN:

841679

Other (OTH)

AF:

0.262

AC:

12050

AN:

46066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

6982

13964

20945

27927

34909

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7002

14004

21006

28008

35010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.268

AC:

29604

AN:

110600

Hom.:

3298

Cov.:

AF XY:

0.263

AC XY:

8661

AN XY:

32914

show subpopulations

African (AFR)

AF:

0.277

AC:

8432

AN:

30429

American (AMR)

AF:

0.477

AC:

4992

AN:

10468

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

489

AN:

2634

East Asian (EAS)

AF:

0.613

AC:

2088

AN:

3404

South Asian (SAS)

AF:

0.375

AC:

952

AN:

2537

European-Finnish (FIN)

AF:

0.135

AC:

808

AN:

6007

Middle Eastern (MID)

AF:

0.220

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.213

AC:

11252

AN:

52725

Other (OTH)

AF:

0.263

AC:

396

AN:

1508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

707

1413

2120

2826

3533

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

300

600

900

1200

1500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.260

Hom.:

5630

Bravo

AF:

0.299

EpiCase

AF:

0.217

EpiControl

AF:

0.212

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Hearing loss, X-linked 6 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.3

(source)

DANN

Benign

0.47

PhyloP100

-0.25

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs5973851

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over