Variant 4-4274372-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000343470.9(LYAR):c.827C>T(p.Ser276Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000864 in 1,608,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

LYAR
ENST00000343470.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.514

Variant links:

Genes affected

LYAR (HGNC:26021): (Ly1 antibody reactive) Enables several functions, including DNA-binding transcription factor binding activity; identical protein binding activity; and transcription regulator inhibitor activity. Involved in several processes, including erythrocyte development; negative regulation of innate immune response; and regulation of transcription, DNA-templated. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LYAR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.015770972).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LYAR	NM_017816.3 linkuse as main transcript	c.827C>T	p.Ser276Leu	missense_variant	7/10	ENST00000343470.9	NP_060286.1
LYAR	NM_001145725.2 linkuse as main transcript	c.827C>T	p.Ser276Leu	missense_variant	7/10		NP_001139197.1
LYAR	XM_011513505.2 linkuse as main transcript	c.827C>T	p.Ser276Leu	missense_variant	7/10		XP_011511807.1
LYAR	XM_011513506.4 linkuse as main transcript	c.827C>T	p.Ser276Leu	missense_variant	6/9		XP_011511808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYAR	ENST00000343470.9 linkuse as main transcript	c.827C>T	p.Ser276Leu	missense_variant	7/10	1	NM_017816.3	ENSP00000345917	P1
LYAR	ENST00000452476.5 linkuse as main transcript	c.827C>T	p.Ser276Leu	missense_variant	7/10	1		ENSP00000397367	P1

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

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:

0.0000735

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000134

AC:

AN:

246996

Hom.:

AF XY:

0.000127

AC XY:

AN XY:

133470

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.0000297

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000676

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000893

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000700

AC:

102

AN:

1456348

Hom.:

Cov.:

AF XY:

0.0000705

AC XY:

AN XY:

723886

show subpopulations

Gnomad4 AFR exome

AF:

0.000961

Gnomad4 AMR exome

AF:

0.0000455

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000468

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000424

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000243

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.000722

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:

0.0000735

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000114

Hom.:

Bravo

AF:

0.000276

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000181

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 03, 2022

The c.827C>T (p.S276L) alteration is located in exon 7 (coding exon 5) of the LYAR gene. This alteration results from a C to T substitution at nucleotide position 827, causing the serine (S) at amino acid position 276 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.62

CADD

Benign

9.9

DANN

Uncertain

0.98

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.10

M_CAP

Benign

0.0039

MetaRNN

Benign

0.016

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.056

Sift

Benign

0.29

T;T

Sift4G

Benign

0.26

T;T

Vest4

0.16

MVP

0.20

MPC

0.050

ClinPred

0.021

GERP RS

4.4

gMVP

0.073

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