17-38915144-G-A

Position:

chr17-38915144-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The ENST00000318008.11(LASP1):c.610G>A(p.Gly204Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000254 in 1,613,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

LASP1
ENST00000318008.11 missense, splice_region

Scores

Splicing: ADA: 0.9239

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.86

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:

LASP1 (HGNC:):

LASP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3750418).

BS2

High AC in GnomAdExome4 at 38 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LASP1	NM_006148.4 linkuse as main transcript	c.610G>A	p.Gly204Arg	missense_variant, splice_region_variant	6/7	ENST00000318008.11	NP_006139.1	Q14847-1A0A024R1S8
LASP1	NM_001271608.2 linkuse as main transcript	c.442G>A	p.Gly148Arg	missense_variant, splice_region_variant	5/6		NP_001258537.1	Q14847-3B4DIC4
LASP1	XM_047435965.1 linkuse as main transcript	c.502G>A	p.Gly168Arg	missense_variant, splice_region_variant	6/7		XP_047291921.1
LASP1	NR_073384.2 linkuse as main transcript	n.912G>A		splice_region_variant, non_coding_transcript_exon_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LASP1	ENST00000318008.11 linkuse as main transcript	c.610G>A	p.Gly204Arg	missense_variant, splice_region_variant	6/7	1	NM_006148.4	ENSP00000325240.6		Q14847-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249584

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135050

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1461320

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

726988

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2024

The c.610G>A (p.G204R) alteration is located in exon 6 (coding exon 6) of the LASP1 gene. This alteration results from a G to A substitution at nucleotide position 610, causing the glycine (G) at amino acid position 204 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.067

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.52

.;D;D;.

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;.;D;T

M_CAP

Benign

0.033

MetaRNN

Benign

0.38

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.6

.;L;L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.7

D;D;D;.

REVEL

Benign

0.15

Sift

Uncertain

0.021

D;D;D;.

Sift4G

Benign

0.14

T;T;T;D

Polyphen

0.94

.;P;P;.

Vest4

0.62

MutPred

0.28

.;Gain of MoRF binding (P = 0.0123);Gain of MoRF binding (P = 0.0123);.;

MVP

0.38

MPC

2.2

ClinPred

0.95

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.92

dbscSNV1_RF

Pathogenic

0.80

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