9-36105267-A-G

Position:

• chr9-36105267-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 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. Variant has been reported in Lovd as Benign (no stars).

• 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

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 9-36105267-A-G is Benign according to our data. Variant chr9-36105267-A-G is described in Lovd as [Benign].
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RECK	NM_021111.3	c.1560A>G	p.Pro520Pro	synonymous_variant	13/21	ENST00000377966.4	NP_066934.1
RECK	NM_001316345.2	c.1176A>G	p.Pro392Pro	synonymous_variant	15/23		NP_001303274.1
RECK	XM_017015207.2	c.1449A>G	p.Pro483Pro	synonymous_variant	14/22		XP_016870696.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RECK	ENST00000377966.4	c.1560A>G	p.Pro520Pro	synonymous_variant	13/21	1	NM_021111.3	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

GnomAD3 exomes AF: 0.339 AC: 85150 AN: 251384 Hom.: 15703 AF XY: 0.351 AC XY: 47734 AN XY: 135862

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 SAS exome AF: 0.368

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

Gnomad4 AFR exome AF: 0.0843

Gnomad4 AMR exome AF: 0.236

Gnomad4 ASJ exome AF: 0.463

Gnomad4 EAS exome AF: 0.269

Gnomad4 SAS exome AF: 0.372

Gnomad4 FIN exome AF: 0.358

Gnomad4 NFE exome AF: 0.397

Gnomad4 OTH exome AF: 0.374

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

Gnomad4 AFR AF: 0.0970

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.336

Alfa AF: 0.380 Hom.: 22540

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	1.6
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

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