NM_017773.4:c.213C>T

Variant names:

• chr1-203771380-C-T
• rs112115396
• NM_017773.4:c.213C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.38
• Publications: 1 publications found

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]

ENSG00000294708 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 29 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017773.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAX1	NM_017773.4	MANE Select	c.213C>T	p.Tyr71Tyr	synonymous	Exon 3 of 5	NP_060243.2	Q8IWV1-1
	LAX1	NM_001136190.2		c.165C>T	p.Tyr55Tyr	synonymous	Exon 3 of 5	NP_001129662.1	Q8IWV1-3
	LAX1	NM_001282878.1		c.-16C>T		5_prime_UTR	Exon 3 of 5	NP_001269807.1	Q8IWV1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAX1	ENST00000442561.7	TSL:1 MANE Select	c.213C>T	p.Tyr71Tyr	synonymous	Exon 3 of 5	ENSP00000406970.2	Q8IWV1-1
	LAX1	ENST00000367215.1	TSL:1	n.183C>T		non_coding_transcript_exon	Exon 3 of 5
	LAX1	ENST00000367217.6	TSL:2	c.165C>T	p.Tyr55Tyr	synonymous	Exon 3 of 5	ENSP00000356186.5	Q8IWV1-3

Frequencies

GnomAD3 genomes AF: 0.00767 AC: 1167 AN: 152162 Hom.: 29 Cov.: 31

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

GnomAD2 exomes AF: 0.00210 AC: 528 AN: 251478 AF XY: 0.00163

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 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.: 21 Cov.: 31 AF XY: 0.000724 AC XY: 526 AN XY: 726334

African (AFR) AF: 0.0268 AC: 897 AN: 33418

American (AMR) AF: 0.00181 AC: 81 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00416 AC: 24 AN: 5768

European-Non Finnish (NFE) AF: 0.000114 AC: 126 AN: 1110044

Other (OTH) AF: 0.00166 AC: 100 AN: 60316

GnomAD4 genome AF: 0.00770 AC: 1172 AN: 152280 Hom.: 29 Cov.: 31 AF XY: 0.00732 AC XY: 545 AN XY: 74444

African (AFR) AF: 0.0265 AC: 1102 AN: 41556

American (AMR) AF: 0.00255 AC: 39 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000220 AC: 15 AN: 68034

Other (OTH) AF: 0.00710 AC: 15 AN: 2112

Alfa AF: 0.00287 Hom.: 3

Bravo AF: 0.00872

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	5.8
DANN	Benign	0.57
PhyloP100		1.4
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs112115396; hg19: chr1-203740508;