rs16932912

Variant names:

• chr9-36087879-G-A
• rs16932912
• NM_021111.3:c.823G>A
• RECK p.Val275Ile

Variant summary

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

The NM_021111.3(RECK):​c.823G>A​(p.Val275Ile) variant causes a missense change. The variant allele was found at a frequency of 0.076 in 1,613,484 control chromosomes in the GnomAD database, including 5,711 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.087 (702 hom., cov: 32)
  • Exomes 𝑓: 0.075 (5009 hom.)
• Consequence: RECK NM_021111.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.94
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016192198).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.282 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECK	NM_021111.3	MANE Select	c.823G>A	p.Val275Ile	missense	Exon 9 of 21	NP_066934.1	O95980
	RECK	NM_001316345.2		c.439G>A	p.Val147Ile	missense	Exon 11 of 23	NP_001303274.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECK	ENST00000377966.4	TSL:1 MANE Select	c.823G>A	p.Val275Ile	missense	Exon 9 of 21	ENSP00000367202.3	O95980
	RECK	ENST00000905834.1		c.823G>A	p.Val275Ile	missense	Exon 9 of 21	ENSP00000575893.1
	RECK	ENST00000943609.1		c.751G>A	p.Val251Ile	missense	Exon 9 of 21	ENSP00000613668.1

Frequencies

GnomAD3 genomes AF: 0.0867 AC: 13184 AN: 152060 Hom.: 703 Cov.: 32

Gnomad AFR AF: 0.0924

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.0868

Gnomad ASJ AF: 0.0695

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.0830

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0641

Gnomad OTH AF: 0.0865

GnomAD2 exomes AF: 0.0921 AC: 23131 AN: 251154 AF XY: 0.0882

Gnomad AFR exome AF: 0.0915

Gnomad AMR exome AF: 0.0949

Gnomad ASJ exome AF: 0.0751

Gnomad EAS exome AF: 0.306

Gnomad FIN exome AF: 0.107

Gnomad NFE exome AF: 0.0628

Gnomad OTH exome AF: 0.0793

GnomAD4 exome AF: 0.0749 AC: 109467 AN: 1461306 Hom.: 5009 Cov.: 32 AF XY: 0.0740 AC XY: 53781 AN XY: 726984

African (AFR) AF: 0.0935 AC: 3128 AN: 33450

American (AMR) AF: 0.0936 AC: 4187 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0737 AC: 1927 AN: 26130

East Asian (EAS) AF: 0.259 AC: 10285 AN: 39684

South Asian (SAS) AF: 0.0672 AC: 5799 AN: 86250

European-Finnish (FIN) AF: 0.104 AC: 5557 AN: 53412

Middle Eastern (MID) AF: 0.0548 AC: 316 AN: 5762

European-Non Finnish (NFE) AF: 0.0662 AC: 73622 AN: 1111532

Other (OTH) AF: 0.0770 AC: 4646 AN: 60376

GnomAD4 genome AF: 0.0867 AC: 13199 AN: 152178 Hom.: 702 Cov.: 32 AF XY: 0.0891 AC XY: 6631 AN XY: 74398

African (AFR) AF: 0.0925 AC: 3841 AN: 41506

American (AMR) AF: 0.0870 AC: 1331 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0695 AC: 241 AN: 3470

East Asian (EAS) AF: 0.294 AC: 1518 AN: 5164

South Asian (SAS) AF: 0.0824 AC: 397 AN: 4818

European-Finnish (FIN) AF: 0.109 AC: 1158 AN: 10600

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0641 AC: 4359 AN: 68004

Other (OTH) AF: 0.0851 AC: 180 AN: 2114

Alfa AF: 0.0738 Hom.: 1846

Bravo AF: 0.0886

Asia WGS AF: 0.149 AC: 516 AN: 3478

EpiCase AF: 0.0596

EpiControl AF: 0.0599

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		4.9
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.13
Sift	Benign	0.33	T
Sift4G	Benign	0.42	T
Varity_R		0.055
gMVP		0.11
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs16932912;

hg19: chr9-36087876;

COSMIC: COSV65035455;

COSMIC: COSV65035455;