chr9-36105267-A-G

Variant names:

• chr9-36105267-A-G
• rs11788747
• NM_021111.3:c.1560A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_021111.3(RECK):​c.1560A>G​(p.Pro520Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 1,612,830 control chromosomes in the GnomAD database, including 116,342 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 0.30 (7994 hom., cov: 31)
  • Exomes 𝑓: 0.38 (108348 hom.)
• Consequence: RECK NM_021111.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.58
• Publications: 34 publications found

Genes affected

RECK (HGNC:11345): (reversion inducing cysteine rich protein with kazal motifs) The protein encoded by this gene is a cysteine-rich, extracellular protein with protease inhibitor-like domains whose expression is suppressed strongly in many tumors and cells transformed by various kinds of oncogenes. In normal cells, this membrane-anchored glycoprotein may serve as a negative regulator for matrix metalloproteinase-9, a key enzyme involved in tumor invasion and metastasis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=-2.58 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021111.3. 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
	RECK	NM_021111.3	MANE Select	c.1560A>G	p.Pro520Pro	synonymous	Exon 13 of 21	NP_066934.1
	RECK	NM_001316345.2		c.1176A>G	p.Pro392Pro	synonymous	Exon 15 of 23	NP_001303274.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECK	ENST00000377966.4	TSL:1 MANE Select	c.1560A>G	p.Pro520Pro	synonymous	Exon 13 of 21	ENSP00000367202.3

Frequencies

GnomAD3 genomes AF: 0.296 AC: 45026 AN: 152028 Hom.: 7996 Cov.: 31

Gnomad AFR AF: 0.0973

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.339

GnomAD2 exomes AF: 0.339 AC: 85150 AN: 251384 AF XY: 0.351

Gnomad AFR exome AF: 0.0878

Gnomad AMR exome AF: 0.229

Gnomad ASJ exome AF: 0.464

Gnomad EAS exome AF: 0.254

Gnomad FIN exome AF: 0.349

Gnomad NFE exome AF: 0.399

Gnomad OTH exome AF: 0.369

GnomAD4 exome AF: 0.379 AC: 554118 AN: 1460684 Hom.: 108348 Cov.: 36 AF XY: 0.381 AC XY: 277026 AN XY: 726692

African (AFR) AF: 0.0843 AC: 2821 AN: 33466

American (AMR) AF: 0.236 AC: 10542 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 12094 AN: 26120

East Asian (EAS) AF: 0.269 AC: 10670 AN: 39650

South Asian (SAS) AF: 0.372 AC: 32102 AN: 86224

European-Finnish (FIN) AF: 0.358 AC: 19101 AN: 53402

Middle Eastern (MID) AF: 0.478 AC: 2759 AN: 5766

European-Non Finnish (NFE) AF: 0.397 AC: 441445 AN: 1110994

Other (OTH) AF: 0.374 AC: 22584 AN: 60348

GnomAD4 genome AF: 0.296 AC: 45012 AN: 152146 Hom.: 7994 Cov.: 31 AF XY: 0.296 AC XY: 22049 AN XY: 74378

African (AFR) AF: 0.0970 AC: 4030 AN: 41526

American (AMR) AF: 0.285 AC: 4349 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1625 AN: 3468

East Asian (EAS) AF: 0.262 AC: 1360 AN: 5184

South Asian (SAS) AF: 0.362 AC: 1744 AN: 4814

European-Finnish (FIN) AF: 0.349 AC: 3693 AN: 10588

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.399 AC: 27131 AN: 67978

Other (OTH) AF: 0.336 AC: 710 AN: 2114

Alfa AF: 0.361 Hom.: 32635

Bravo AF: 0.279

Asia WGS AF: 0.288 AC: 1007 AN: 3478

EpiCase AF: 0.412

EpiControl AF: 0.406

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	1.6
DANN	Benign	0.64
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11788747; hg19: chr9-36105264; COSMIC: COSV65035312;