rs2242312

Variant names:

• chr11-130405451-G-A
• rs2242312
• NM_007037.6:c.*107C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-130405451-G-A
• chr11-130405451-G-C
• chr11-130405451-G-T

Variant summary

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

The NM_007037.6(ADAMTS8):​c.*107C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0825 in 1,498,332 control chromosomes in the GnomAD database, including 6,452 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 0.12 (1374 hom., cov: 32)
  • Exomes 𝑓: 0.079 (5078 hom.)
• Consequence: ADAMTS8 NM_007037.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129
• Publications: 9 publications found

Genes affected

ADAMTS8 (HGNC:224): (ADAM metallopeptidase with thrombospondin type 1 motif 8) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the family 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 enzyme. This enzyme contains two C-terminal TS motifs, and disrupts angiogenesis in vivo. A number of disorders have been mapped in the vicinity of this gene, most notably lung neoplasms. Reduced expression of this gene has been observed in multiple human cancers and this gene has been proposed as a potential tumor suppressor. [provided by RefSeq, Feb 2016]

ZBTB44-DT (HGNC:54265): (ZBTB44 divergent transcript)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007037.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS8	NM_007037.6	MANE Select	c.*107C>T		3_prime_UTR	Exon 9 of 9	NP_008968.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTS8	ENST00000257359.7	TSL:1 MANE Select	c.*107C>T		3_prime_UTR	Exon 9 of 9	ENSP00000257359.6
	ADAMTS8	ENST00000531752.1	TSL:2	n.1724C>T		non_coding_transcript_exon	Exon 4 of 4
	ZBTB44-DT	ENST00000777858.1		n.320+11652G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17869 AN: 152068 Hom.: 1372 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0968

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0532

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0695

Gnomad OTH AF: 0.113

GnomAD4 exome AF: 0.0786 AC: 105762 AN: 1346146 Hom.: 5078 Cov.: 30 AF XY: 0.0797 AC XY: 52507 AN XY: 658784

African (AFR) AF: 0.210 AC: 6307 AN: 30062

American (AMR) AF: 0.0769 AC: 2205 AN: 28672

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 2676 AN: 19846

East Asian (EAS) AF: 0.200 AC: 7747 AN: 38680

South Asian (SAS) AF: 0.117 AC: 8094 AN: 69100

European-Finnish (FIN) AF: 0.0524 AC: 1927 AN: 36756

Middle Eastern (MID) AF: 0.102 AC: 375 AN: 3686

European-Non Finnish (NFE) AF: 0.0671 AC: 71335 AN: 1063634

Other (OTH) AF: 0.0915 AC: 5096 AN: 55710

GnomAD4 genome AF: 0.118 AC: 17894 AN: 152186 Hom.: 1374 Cov.: 32 AF XY: 0.116 AC XY: 8613 AN XY: 74394

African (AFR) AF: 0.210 AC: 8734 AN: 41512

American (AMR) AF: 0.0968 AC: 1480 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 463 AN: 3470

East Asian (EAS) AF: 0.207 AC: 1068 AN: 5150

South Asian (SAS) AF: 0.121 AC: 583 AN: 4826

European-Finnish (FIN) AF: 0.0532 AC: 564 AN: 10608

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0695 AC: 4724 AN: 68018

Other (OTH) AF: 0.114 AC: 239 AN: 2102

Alfa AF: 0.0853 Hom.: 3037

Bravo AF: 0.126

Asia WGS AF: 0.144 AC: 501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.52
PhyloP100		0.13
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: rs2242312; hg19: chr11-130275346;