rs4878639

Variant names:

• chr9-36099402-T-C
• rs4878639
• NM_021111.3:c.1086-929T>C

Variant summary

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

The NM_021111.3(RECK):​c.1086-929T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,228 control chromosomes in the GnomAD database, including 4,055 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 0.21 (4055 hom., cov: 32)
• Consequence: RECK NM_021111.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344
• Publications: 7 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 (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECK	NM_021111.3	c.1086-929T>C		intron_variant	Intron 10 of 20	ENST00000377966.4	NP_066934.1
RECK	NM_001316345.2	c.702-929T>C		intron_variant	Intron 12 of 22		NP_001303274.1
RECK	XM_017015207.2	c.975-929T>C		intron_variant	Intron 11 of 21		XP_016870696.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECK	ENST00000377966.4	c.1086-929T>C		intron_variant	Intron 10 of 20	1	NM_021111.3	ENSP00000367202.3

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31276 AN: 152110 Hom.: 4053 Cov.: 32

Gnomad AFR AF: 0.0508

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.230

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.205 AC: 31272 AN: 152228 Hom.: 4055 Cov.: 32 AF XY: 0.208 AC XY: 15483 AN XY: 74414

African (AFR) AF: 0.0506 AC: 2105 AN: 41560

American (AMR) AF: 0.202 AC: 3090 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1128 AN: 3472

East Asian (EAS) AF: 0.261 AC: 1352 AN: 5190

South Asian (SAS) AF: 0.303 AC: 1464 AN: 4824

European-Finnish (FIN) AF: 0.236 AC: 2495 AN: 10582

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18885 AN: 67992

Other (OTH) AF: 0.228 AC: 483 AN: 2116

Alfa AF: 0.240 Hom.: 8091

Bravo AF: 0.191

Asia WGS AF: 0.253 AC: 883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.98
DANN	Benign	0.60
PhyloP100		-0.34
Mutation Taster		=100/0	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: rs4878639; hg19: chr9-36099399;