Genetic Variant LAX1:p.Tyr71Tyr (chr1-203771380-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_017773.4(LAX1):c.213C>T(p.Tyr71Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,611,994 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0077 ( 29 hom., cov: 31)

Exomes 𝑓: 0.00084 ( 21 hom. )

Consequence

LAX1
NM_017773.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.38

Variant links:

Genes affected

LAX1 (HGNC:26005): (lymphocyte transmembrane adaptor 1) Enables SH2 domain binding activity and protein kinase binding activity. Involved in several processes, including B cell activation; negative regulation of MAP kinase activity; and negative regulation of T cell activation. Located in Golgi apparatus; cytosol; and plasma membrane. Is integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LAX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 1-203771380-C-T is Benign according to our data. Variant chr1-203771380-C-T is described in ClinVar as [Benign]. Clinvar id is 789554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.38 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0077 (1172/152280) while in subpopulation AFR AF= 0.0265 (1102/41556). AF 95% confidence interval is 0.0252. There are 29 homozygotes in gnomad4. There are 545 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAX1	NM_017773.4 link	c.213C>T	p.Tyr71Tyr	synonymous_variant	Exon 3 of 5	ENST00000442561.7	NP_060243.2	Q8IWV1-1
LAX1	NM_001136190.2 link	c.165C>T	p.Tyr55Tyr	synonymous_variant	Exon 3 of 5		NP_001129662.1	Q8IWV1-3
LAX1	XM_006711397.4 link	c.213C>T	p.Tyr71Tyr	synonymous_variant	Exon 4 of 6		XP_006711460.1	Q8IWV1-1
LAX1	NM_001282878.1 link	c.-16C>T		5_prime_UTR_variant	Exon 3 of 5		NP_001269807.1	Q8IWV1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LAX1	ENST00000442561.7 link	c.213C>T	p.Tyr71Tyr	synonymous_variant	Exon 3 of 5	1	NM_017773.4	ENSP00000406970.2	Q8IWV1-1
LAX1	ENST00000367215.1 link	n.183C>T		non_coding_transcript_exon_variant	Exon 3 of 5	1
LAX1	ENST00000367217.5 link	c.165C>T	p.Tyr55Tyr	synonymous_variant	Exon 3 of 5	2		ENSP00000356186.5	Q8IWV1-3

Frequencies

GnomAD3 genomes

AF:

0.00767

AC:

1167

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00210

AC:

528

AN:

251478

Hom.:

AF XY:

0.00163

AC XY:

221

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.0273

Gnomad AMR exome

AF:

0.00171

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000842

AC:

1229

AN:

1459714

Hom.:

Cov.:

AF XY:

0.000724

AC XY:

526

AN XY:

726334

show subpopulations

Gnomad4 AFR exome

AF:

0.0268

Gnomad4 AMR exome

AF:

0.00181

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:

0.000114

Gnomad4 OTH exome

AF:

0.00166

GnomAD4 genome

AF:

0.00770

AC:

1172

AN:

152280

Hom.:

Cov.:

AF XY:

0.00732

AC XY:

545

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0265

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00307

Hom.:

Bravo

AF:

0.00872

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 30, 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_noAF

Benign

-0.44

CADD

Benign

5.8

DANN

Benign

0.57

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