5-5146110-G-C

Variant names:

• chr5-5146110-G-C
• rs1871468
• NM_139056.4:c.176-20G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139056.4(ADAMTS16):​c.176-20G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 1,602,686 control chromosomes in the GnomAD database, including 576,022 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.82 (51478 hom., cov: 33)
  • Exomes 𝑓: 0.85 (524544 hom.)
• Consequence: ADAMTS16 NM_139056.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.361
• Publications: 7 publications found

Genes affected

ADAMTS16 (HGNC:17108): (ADAM metallopeptidase with thrombospondin type 1 motif 16) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. ADAMTS family members share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature protein, which may inhibit chondrosarcoma cell proliferation and migration. This gene may regulate blood pressure. [provided by RefSeq, May 2016]

ENSG00000250866 (HGNC:58093):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.879 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS16	NM_139056.4	c.176-20G>C		intron_variant	Intron 2 of 22	ENST00000274181.7	NP_620687.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS16	ENST00000274181.7	c.176-20G>C		intron_variant	Intron 2 of 22	2	NM_139056.4	ENSP00000274181.7
ADAMTS16	ENST00000511368.5	c.176-20G>C		intron_variant	Intron 2 of 10	1		ENSP00000421631.1
ADAMTS16	ENST00000433402.2	n.176-20G>C		intron_variant	Intron 2 of 19	1
ENSG00000250866	ENST00000514848.1	n.221-3739C>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124721 AN: 152094 Hom.: 51440 Cov.: 33

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.874

Gnomad AMR AF: 0.891

Gnomad ASJ AF: 0.942

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.874

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.851

Gnomad OTH AF: 0.850

GnomAD2 exomes AF: 0.839 AC: 206733 AN: 246458 AF XY: 0.842

Gnomad AFR exome AF: 0.752

Gnomad AMR exome AF: 0.913

Gnomad ASJ exome AF: 0.938

Gnomad EAS exome AF: 0.635

Gnomad FIN exome AF: 0.789

Gnomad NFE exome AF: 0.848

Gnomad OTH exome AF: 0.859

GnomAD4 exome AF: 0.849 AC: 1231123 AN: 1450472 Hom.: 524544 Cov.: 30 AF XY: 0.850 AC XY: 612230 AN XY: 720072

African (AFR) AF: 0.750 AC: 24942 AN: 33260

American (AMR) AF: 0.911 AC: 40517 AN: 44474

Ashkenazi Jewish (ASJ) AF: 0.942 AC: 24388 AN: 25898

East Asian (EAS) AF: 0.639 AC: 25233 AN: 39474

South Asian (SAS) AF: 0.882 AC: 75824 AN: 85966

European-Finnish (FIN) AF: 0.792 AC: 42114 AN: 53178

Middle Eastern (MID) AF: 0.930 AC: 5327 AN: 5728

European-Non Finnish (NFE) AF: 0.854 AC: 941848 AN: 1102622

Other (OTH) AF: 0.851 AC: 50930 AN: 59872

GnomAD4 genome AF: 0.820 AC: 124817 AN: 152214 Hom.: 51478 Cov.: 33 AF XY: 0.817 AC XY: 60785 AN XY: 74424

African (AFR) AF: 0.750 AC: 31125 AN: 41514

American (AMR) AF: 0.892 AC: 13638 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.942 AC: 3269 AN: 3472

East Asian (EAS) AF: 0.645 AC: 3335 AN: 5174

South Asian (SAS) AF: 0.875 AC: 4218 AN: 4820

European-Finnish (FIN) AF: 0.797 AC: 8455 AN: 10608

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.852 AC: 57919 AN: 68018

Other (OTH) AF: 0.850 AC: 1791 AN: 2106

Alfa AF: 0.843 Hom.: 6044

Bravo AF: 0.826

Asia WGS AF: 0.730 AC: 2540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.59
DANN	Benign	0.49
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1871468; hg19: chr5-5146223; COSMIC: COSV107274609;