rs10972727

Positions:

• chr9-36110066-T-A
• chr9-36110066-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_021111.3(RECK):​c.1875T>A​(p.Arg625=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,606,556 control chromosomes in the GnomAD database, including 103,114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.28 (7259 hom., cov: 32)
  • Exomes 𝑓: 0.36 (95855 hom.)
• Consequence: RECK NM_021111.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.918

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 9-36110066-T-A is Benign according to our data. Variant chr9-36110066-T-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.918 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RECK	NM_021111.3	c.1875T>A	p.Arg625=	synonymous_variant	15/21	ENST00000377966.4	NP_066934.1
RECK	NM_001316345.2	c.1491T>A	p.Arg497=	synonymous_variant	17/23		NP_001303274.1
RECK	XM_017015207.2	c.1764T>A	p.Arg588=	synonymous_variant	16/22		XP_016870696.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RECK	ENST00000377966.4	c.1875T>A	p.Arg625=	synonymous_variant	15/21	1	NM_021111.3	ENSP00000367202	P1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42751 AN: 152018 Hom.: 7261 Cov.: 32

Gnomad AFR AF: 0.0923

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.322

GnomAD3 exomes AF: 0.323 AC: 81055 AN: 251228 Hom.: 14212 AF XY: 0.335 AC XY: 45451 AN XY: 135766

Gnomad AFR exome AF: 0.0835

Gnomad AMR exome AF: 0.218

Gnomad ASJ exome AF: 0.451

Gnomad EAS exome AF: 0.254

Gnomad SAS exome AF: 0.354

Gnomad FIN exome AF: 0.341

Gnomad NFE exome AF: 0.375

Gnomad OTH exome AF: 0.345

GnomAD4 exome AF: 0.358 AC: 520514 AN: 1454420 Hom.: 95855 Cov.: 34 AF XY: 0.360 AC XY: 259789 AN XY: 721896

Gnomad4 AFR exome AF: 0.0810

Gnomad4 AMR exome AF: 0.225

Gnomad4 ASJ exome AF: 0.450

Gnomad4 EAS exome AF: 0.269

Gnomad4 SAS exome AF: 0.358

Gnomad4 FIN exome AF: 0.348

Gnomad4 NFE exome AF: 0.373

Gnomad4 OTH exome AF: 0.355

GnomAD4 genome AF: 0.281 AC: 42738 AN: 152136 Hom.: 7259 Cov.: 32 AF XY: 0.283 AC XY: 21019 AN XY: 74368

Gnomad4 AFR AF: 0.0921

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.319

Alfa AF: 0.358 Hom.: 3403

Bravo AF: 0.264

Asia WGS AF: 0.281 AC: 981 AN: 3478

EpiCase AF: 0.389

EpiControl AF: 0.382

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	5.3
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs10972727; hg19: chr9-36110063; COSMIC: COSV65035313;