Variant chr9-36058819-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_021111.3(RECK):c.160-8T>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,578,842 control chromosomes in the GnomAD database, including 143 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0083 ( 7 hom., cov: 30)

Exomes 𝑓: 0.013 ( 136 hom. )

Consequence

RECK
NM_021111.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.005283

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.127

Variant links:

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]

RECK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 9-36058819-T-G is Benign according to our data. Variant chr9-36058819-T-G is described in ClinVar as [Benign]. Clinvar id is 770385.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.013 (18533/1428246) while in subpopulation NFE AF= 0.0155 (16943/1095510). AF 95% confidence interval is 0.0153. There are 136 homozygotes in gnomad4_exome. There are 9072 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RECK	NM_021111.3 linkuse as main transcript	c.160-8T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000377966.4

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
RECK	ENST00000377966.4 linkuse as main transcript	c.160-8T>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_021111.3	P1
RECK	ENST00000479053.1 linkuse as main transcript	n.219-8T>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	1
RECK	ENST00000475774.5 linkuse as main transcript	n.269-8T>G	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.00834

AC:

1255

AN:

150480

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00295

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00489

Gnomad ASJ

AF:

0.00174

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00335

Gnomad FIN

AF:

0.00387

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0146

Gnomad OTH

AF:

0.00531

GnomAD3 exomes

AF:

0.00771

AC:

1763

AN:

228778

Hom.:

AF XY:

0.00801

AC XY:

998

AN XY:

124522

show subpopulations

Gnomad AFR exome

AF:

0.00218

Gnomad AMR exome

AF:

0.00429

Gnomad ASJ exome

AF:

0.00155

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00410

Gnomad FIN exome

AF:

0.00494

Gnomad NFE exome

AF:

0.0126

Gnomad OTH exome

AF:

0.00666

GnomAD4 exome

AF:

0.0130

AC:

18533

AN:

1428246

Hom.:

136

Cov.:

AF XY:

0.0128

AC XY:

9072

AN XY:

710704

show subpopulations

Gnomad4 AFR exome

AF:

0.00200

Gnomad4 AMR exome

AF:

0.00483

Gnomad4 ASJ exome

AF:

0.00186

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00398

Gnomad4 FIN exome

AF:

0.00458

Gnomad4 NFE exome

AF:

0.0155

Gnomad4 OTH exome

AF:

0.0122

GnomAD4 genome

AF:

0.00834

AC:

1256

AN:

150596

Hom.:

Cov.:

AF XY:

0.00724

AC XY:

533

AN XY:

73592

show subpopulations

Gnomad4 AFR

AF:

0.00294

Gnomad4 AMR

AF:

0.00489

Gnomad4 ASJ

AF:

0.00174

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00336

Gnomad4 FIN

AF:

0.00387

Gnomad4 NFE

AF:

0.0146

Gnomad4 OTH

AF:

0.00573

Alfa

AF:

0.0133

Hom.:

Bravo

AF:

0.00828

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.6

DANN

Benign

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0053

dbscSNV1_RF

Benign

0.18

SpliceAI score (max)

0.19

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over