Genetic Variant COL16A1:p.Arg90Arg (chr1-31698605-T-G) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001856.4(COL16A1):c.268A>C(p.Arg90Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 1,613,432 control chromosomes in the GnomAD database, including 336,174 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.67 ( 34998 hom., cov: 32)

Exomes 𝑓: 0.64 ( 301176 hom. )

Consequence

COL16A1
NM_001856.4 splice_region, synonymous

Scores

Splicing: ADA: 0.0005934

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.74

Variant links:

Genes affected

COL16A1 (HGNC:2193): (collagen type XVI alpha 1 chain) This gene encodes the alpha chain of type XVI collagen, a member of the FACIT collagen family (fibril-associated collagens with interrupted helices). Members of this collagen family are found in association with fibril-forming collagens such as type I and II, and serve to maintain the integrity of the extracellular matrix. High levels of type XVI collagen have been found in fibroblasts and keratinocytes, and in smooth muscle and amnion. [provided by RefSeq, Jul 2008]

COL16A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP7

Synonymous conserved (PhyloP=1.74 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL16A1	NM_001856.4 link	c.268A>C	p.Arg90Arg	splice_region_variant, synonymous_variant	Exon 5 of 71	ENST00000373672.8	NP_001847.3	Q07092-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
COL16A1	ENST00000373672.8 link	c.268A>C	p.Arg90Arg	splice_region_variant, synonymous_variant	Exon 5 of 71	5	NM_001856.4	ENSP00000362776.3	Q07092-1
COL16A1	ENST00000373668.7 link	c.268A>C	p.Arg90Arg	splice_region_variant, synonymous_variant	Exon 5 of 41	2		ENSP00000362772.3	A6NCT7
COL16A1	ENST00000532877.1 link	n.419A>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 4 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.672

AC:

102072

AN:

151880

Hom.:

34940

Cov.:

show subpopulations

Gnomad AFR

AF:

0.777

Gnomad AMI

AF:

0.627

Gnomad AMR

AF:

0.635

Gnomad ASJ

AF:

0.577

Gnomad EAS

AF:

0.333

Gnomad SAS

AF:

0.613

Gnomad FIN

AF:

0.641

Gnomad MID

AF:

0.582

Gnomad NFE

AF:

0.657

Gnomad OTH

AF:

0.662

GnomAD3 exomes

AF:

0.619

AC:

154178

AN:

248896

Hom.:

49043

AF XY:

0.620

AC XY:

83761

AN XY:

135048

show subpopulations

Gnomad AFR exome

AF:

0.790

Gnomad AMR exome

AF:

0.590

Gnomad ASJ exome

AF:

0.575

Gnomad EAS exome

AF:

0.324

Gnomad SAS exome

AF:

0.610

Gnomad FIN exome

AF:

0.646

Gnomad NFE exome

AF:

0.653

Gnomad OTH exome

AF:

0.631

GnomAD4 exome

AF:

0.639

AC:

933690

AN:

1461434

Hom.:

301176

Cov.:

AF XY:

0.639

AC XY:

464235

AN XY:

726998

show subpopulations

Gnomad4 AFR exome

AF:

0.785

Gnomad4 AMR exome

AF:

0.602

Gnomad4 ASJ exome

AF:

0.581

Gnomad4 EAS exome

AF:

0.318

Gnomad4 SAS exome

AF:

0.610

Gnomad4 FIN exome

AF:

0.648

Gnomad4 NFE exome

AF:

0.651

Gnomad4 OTH exome

AF:

0.628

GnomAD4 genome

AF:

0.672

AC:

102189

AN:

151998

Hom.:

34998

Cov.:

AF XY:

0.668

AC XY:

49653

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.778

Gnomad4 AMR

AF:

0.635

Gnomad4 ASJ

AF:

0.577

Gnomad4 EAS

AF:

0.334

Gnomad4 SAS

AF:

0.614

Gnomad4 FIN

AF:

0.641

Gnomad4 NFE

AF:

0.657

Gnomad4 OTH

AF:

0.655

Alfa

AF:

0.629

Hom.:

39457

Bravo

AF:

0.674

Asia WGS

AF:

0.516

AC:

1796

AN:

3478

EpiCase

AF:

0.646

EpiControl

AF:

0.643

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00059

dbscSNV1_RF

Benign

0.034

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over