rs2721173

Positions:

• chr8-144519045-C-T

Variant summary

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

The NM_014665.4(LRRC14):​c.-111-570C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,110 control chromosomes in the GnomAD database, including 15,204 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 0.44 (15204 hom., cov: 33)
• Consequence: LRRC14 NM_014665.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

Genes affected

LRRC14 (HGNC:20419): (leucine rich repeat containing 14) This gene encodes a leucine-rich repeat-containing protein. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC14	NM_014665.4	c.-111-570C>T		intron_variant		ENST00000292524.6	NP_055480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC14	ENST00000292524.6	c.-111-570C>T		intron_variant		1	NM_014665.4	ENSP00000292524	P1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66204 AN: 151992 Hom.: 15195 Cov.: 33

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.435 AC: 66242 AN: 152110 Hom.: 15204 Cov.: 33 AF XY: 0.442 AC XY: 32838 AN XY: 74360

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.474

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.478

Gnomad4 OTH AF: 0.466

Alfa AF: 0.457 Hom.: 5902

Bravo AF: 0.430

Asia WGS AF: 0.559 AC: 1943 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.65
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2721173; hg19: chr8-145744429;