rs139736960

Variant names:

• chr19-9966377-C-T
• rs139736960
• NM_015719.4:c.4719G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_015719.4(COL5A3):​c.4719G>A​(p.Arg1573Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00441 in 1,610,094 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0052 (17 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (45 hom.)
• Consequence: COL5A3 NM_015719.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.666
• Publications: 2 publications found

Genes affected

COL5A3 (HGNC:14864): (collagen type V alpha 3 chain) This gene encodes an alpha chain for one of the low abundance fibrillar collagens. Fibrillar collagen molecules are trimers that can be composed of one or more types of alpha chains. Type V collagen is found in tissues containing type I collagen and appears to regulate the assembly of heterotypic fibers composed of both type I and type V collagen. This gene product is closely related to type XI collagen and it is possible that the collagen chains of types V and XI constitute a single collagen type with tissue-specific chain combinations. Mutations in this gene are thought to be responsible for the symptoms of a subset of patients with Ehlers-Danlos syndrome type III. Messages of several sizes can be detected in northern blots but sequence information cannot confirm the identity of the shorter messages. [provided by RefSeq, Jul 2008]

ENSG00000295554 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 19-9966377-C-T is Benign according to our data. Variant chr19-9966377-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2649277.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.666 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 17 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015719.4. 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
	COL5A3	NM_015719.4	MANE Select	c.4719G>A	p.Arg1573Arg	synonymous	Exon 64 of 67	NP_056534.2	P25940

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL5A3	ENST00000264828.4	TSL:1 MANE Select	c.4719G>A	p.Arg1573Arg	synonymous	Exon 64 of 67	ENSP00000264828.3	P25940
	ENSG00000295554	ENST00000730923.1		n.74-17673C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00518 AC: 788 AN: 152162 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0235

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00722

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00580 AC: 1438 AN: 248080 AF XY: 0.00574

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00120

Gnomad ASJ exome AF: 0.00459

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0258

Gnomad NFE exome AF: 0.00660

Gnomad OTH exome AF: 0.00861

GnomAD4 exome AF: 0.00433 AC: 6306 AN: 1457814 Hom.: 45 Cov.: 32 AF XY: 0.00438 AC XY: 3176 AN XY: 724716

African (AFR) AF: 0.000299 AC: 10 AN: 33442

American (AMR) AF: 0.00113 AC: 50 AN: 44396

Ashkenazi Jewish (ASJ) AF: 0.00440 AC: 114 AN: 25900

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.0000584 AC: 5 AN: 85628

European-Finnish (FIN) AF: 0.0261 AC: 1389 AN: 53248

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5754

European-Non Finnish (NFE) AF: 0.00404 AC: 4485 AN: 1109594

Other (OTH) AF: 0.00415 AC: 250 AN: 60216

GnomAD4 genome AF: 0.00517 AC: 788 AN: 152280 Hom.: 17 Cov.: 32 AF XY: 0.00567 AC XY: 422 AN XY: 74476

African (AFR) AF: 0.000337 AC: 14 AN: 41548

American (AMR) AF: 0.000981 AC: 15 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.0235 AC: 249 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00722 AC: 491 AN: 68016

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00557 Hom.: 11

Bravo AF: 0.00275

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	13
DANN	Benign	0.90
PhyloP100		0.67
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs139736960; hg19: chr19-10077053;