4-4275191-C-T

Position:

• chr4-4275191-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017816.3(LYAR):​c.430-422G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 152,146 control chromosomes in the GnomAD database, including 58,951 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.88 (58951 hom., cov: 31)
• Consequence: LYAR NM_017816.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYAR	NM_017816.3	c.430-422G>A		intron_variant		ENST00000343470.9	NP_060286.1
LYAR	NM_001145725.2	c.430-422G>A		intron_variant			NP_001139197.1
LYAR	XM_011513505.2	c.430-422G>A		intron_variant			XP_011511807.1
LYAR	XM_011513506.4	c.430-422G>A		intron_variant			XP_011511808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYAR	ENST00000343470.9	c.430-422G>A		intron_variant		1	NM_017816.3	ENSP00000345917.4
LYAR	ENST00000452476.5	c.430-422G>A		intron_variant		1		ENSP00000397367.1

Frequencies

GnomAD3 genomes AF: 0.879 AC: 133691 AN: 152028 Hom.: 58896 Cov.: 31

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.893

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.891

Gnomad FIN AF: 0.939

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.883

Gnomad OTH AF: 0.861

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.879 AC: 133804 AN: 152146 Hom.: 58951 Cov.: 31 AF XY: 0.883 AC XY: 65693 AN XY: 74412

Gnomad4 AFR AF: 0.846

Gnomad4 AMR AF: 0.893

Gnomad4 ASJ AF: 0.892

Gnomad4 EAS AF: 0.946

Gnomad4 SAS AF: 0.890

Gnomad4 FIN AF: 0.939

Gnomad4 NFE AF: 0.883

Gnomad4 OTH AF: 0.862

Alfa AF: 0.890 Hom.: 14512

Bravo AF: 0.873

Asia WGS AF: 0.917 AC: 3191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.5
DANN	Benign	0.67

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

Other links and lift over

dbSNP: rs2916448; hg19: chr4-4276918;