rs10972727

Variant names:

• chr9-36110066-T-A
• rs10972727
• NM_021111.3:c.1875T>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_021111.3(RECK):​c.1875T>A​(p.Arg625Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 22 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• 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 rank	MANE	Protein	UniProt
RECK	NM_021111.3	c.1875T>A	p.Arg625Arg	synonymous_variant	Exon 15 of 21	ENST00000377966.4	NP_066934.1
RECK	NM_001316345.2	c.1491T>A	p.Arg497Arg	synonymous_variant	Exon 17 of 23		NP_001303274.1
RECK	XM_017015207.2	c.1764T>A	p.Arg588Arg	synonymous_variant	Exon 16 of 22		XP_016870696.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECK	ENST00000377966.4	c.1875T>A	p.Arg625Arg	synonymous_variant	Exon 15 of 21	1	NM_021111.3	ENSP00000367202.3

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

GnomAD2 exomes AF: 0.323 AC: 81055 AN: 251228 AF XY: 0.335

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 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

African (AFR) AF: 0.0810 AC: 2706 AN: 33400

American (AMR) AF: 0.225 AC: 10020 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 11704 AN: 26030

East Asian (EAS) AF: 0.269 AC: 10610 AN: 39500

South Asian (SAS) AF: 0.358 AC: 30813 AN: 86074

European-Finnish (FIN) AF: 0.348 AC: 18570 AN: 53304

Middle Eastern (MID) AF: 0.464 AC: 2665 AN: 5748

European-Non Finnish (NFE) AF: 0.373 AC: 412099 AN: 1105718

Other (OTH) AF: 0.355 AC: 21327 AN: 60024

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

African (AFR) AF: 0.0921 AC: 3824 AN: 41534

American (AMR) AF: 0.270 AC: 4124 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1549 AN: 3470

East Asian (EAS) AF: 0.261 AC: 1350 AN: 5172

South Asian (SAS) AF: 0.351 AC: 1694 AN: 4822

European-Finnish (FIN) AF: 0.342 AC: 3614 AN: 10574

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25558 AN: 67976

Other (OTH) AF: 0.319 AC: 675 AN: 2114

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
PhyloP100		-0.92
Mutation Taster		=99/1	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: rs10972727; hg19: chr9-36110063; COSMIC: COSV65035313;