Genetic Variant LASP1:p.Cys32Cys (chr17-38878112-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001271608.2(LASP1):c.13C>T(p.Arg5*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,613,816 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 14 hom. )

Consequence

LASP1
NM_001271608.2 stop_gained

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.100

Variant links:

Genes affected

LASP1 (HGNC:6513): (LIM and SH3 protein 1) This gene encodes a member of a subfamily of LIM proteins, characterized by a LIM motif and a domain of Src homology region 3, and also a member of the nebulin family of actin-binding proteins. The encoded protein is a cAMP and cGMP dependent signaling protein and binds to the actin cytoskeleton at extensions of the cell membrane. The encoded protein has been linked to metastatic breast cancer, hematopoetic tumors such as B-cell lymphomas, and colorectal cancer. [provided by RefSeq, Oct 2012]

LASP1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 17-38878112-C-T is Benign according to our data. Variant chr17-38878112-C-T is described in ClinVar as [Benign]. Clinvar id is 728929.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 266 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LASP1	NM_006148.4 link	c.96C>T	p.Cys32Cys	synonymous_variant	Exon 2 of 7	ENST00000318008.11	NP_006139.1	Q14847-1A0A024R1S8
LASP1	NM_001271608.2 link	c.13C>T	p.Arg5*	stop_gained	Exon 2 of 6		NP_001258537.1	Q14847-3B4DIC4
LASP1	XM_047435965.1 link	c.-13C>T		5_prime_UTR_variant	Exon 2 of 7		XP_047291921.1
LASP1	NR_073384.2 link	n.228C>T		non_coding_transcript_exon_variant	Exon 2 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LASP1	ENST00000318008.11 link	c.96C>T	p.Cys32Cys	synonymous_variant	Exon 2 of 7	1	NM_006148.4	ENSP00000325240.6		Q14847-1

Frequencies

GnomAD3 genomes

AF:

0.00175

AC:

266

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.0123

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.0140

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00276

AC:

693

AN:

251394

Hom.:

AF XY:

0.00266

AC XY:

361

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.0110

Gnomad SAS exome

AF:

0.00167

Gnomad FIN exome

AF:

0.0142

Gnomad NFE exome

AF:

0.000914

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00137

AC:

2003

AN:

1461544

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

1020

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.0151

Gnomad4 SAS exome

AF:

0.00155

Gnomad4 FIN exome

AF:

0.0148

Gnomad4 NFE exome

AF:

0.000263

Gnomad4 OTH exome

AF:

0.00295

GnomAD4 genome

AF:

0.00175

AC:

266

AN:

152272

Hom.:

Cov.:

AF XY:

0.00230

AC XY:

171

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.0126

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.0140

Gnomad4 NFE

AF:

0.000573

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000833

Hom.:

Bravo

AF:

0.000854

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00282

AC:

343

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 10, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.49

Vest4

0.73

GERP RS

-0.22

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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