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

Variant summary

Our verdict is Likely benign. The variant received -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

Publications

7 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -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 VariationId is 728929.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 266 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271608.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LASP1	NM_006148.4	MANE Select	c.96C>T	p.Cys32Cys	synonymous	Exon 2 of 7	NP_006139.1	Q14847-1
LASP1	NM_001271608.2		c.13C>T	p.Arg5*	stop_gained	Exon 2 of 6	NP_001258537.1	Q14847-3
LASP1	NR_073384.2		n.228C>T		non_coding_transcript_exon	Exon 2 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LASP1	ENST00000318008.11	TSL:1 MANE Select	c.96C>T	p.Cys32Cys	synonymous	Exon 2 of 7	ENSP00000325240.6	Q14847-1
LASP1	ENST00000443937.7	TSL:1	n.96C>T		non_coding_transcript_exon	Exon 2 of 8	ENSP00000414803.3	F6S2S5
LASP1	ENST00000433206.6	TSL:2	c.13C>T	p.Arg5*	stop_gained	Exon 2 of 6	ENSP00000401048.2	Q14847-3

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

GnomAD2 exomes

AF:

0.00276

AC:

693

AN:

251394

AF XY:

0.00266

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 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

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.0000224

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.000344

AC:

AN:

26130

East Asian (EAS)

AF:

0.0151

AC:

598

AN:

39696

South Asian (SAS)

AF:

0.00155

AC:

134

AN:

86232

European-Finnish (FIN)

AF:

0.0148

AC:

788

AN:

53418

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000263

AC:

292

AN:

1111742

Other (OTH)

AF:

0.00295

AC:

178

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

107

214

322

429

536

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00175

AC:

266

AN:

152272

Hom.:

Cov.:

AF XY:

0.00230

AC XY:

171

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41552

American (AMR)

AF:

0.000196

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.0126

AC:

AN:

5178

South Asian (SAS)

AF:

0.000622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0140

AC:

148

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000573

AC:

AN:

68028

Other (OTH)

AF:

0.00190

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00109

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.49

PhyloP100

-0.10

Vest4

0.73

GERP RS

-0.22

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=148/52

disease causing (fs/PTC)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over