8-144522244-T-C

Variant summary

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

The NM_014665.4(LRRC14):c.*766T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 522,390 control chromosomes in the GnomAD database, including 62,074 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 0.49 (18365 hom., cov: 34)
  • Exomes 𝑓: 0.48 (43709 hom.)
• Consequence: LRRC14 NM_014665.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.17

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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC14	NM_014665.4	c.*766T>C		3_prime_UTR_variant	4/4	ENST00000292524.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC14	ENST00000292524.6	c.*766T>C		3_prime_UTR_variant	4/4	1	NM_014665.4	P1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 73658 AN: 150622 Hom.: 18349 Cov.: 34

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.509

GnomAD4 exome AF: 0.483 AC: 179668 AN: 371650 Hom.: 43709 Cov.: 6 AF XY: 0.483 AC XY: 90909 AN XY: 188194

Gnomad4 AFR exome AF: 0.562

Gnomad4 AMR exome AF: 0.388

Gnomad4 ASJ exome AF: 0.604

Gnomad4 EAS exome AF: 0.285

Gnomad4 SAS exome AF: 0.428

Gnomad4 FIN exome AF: 0.459

Gnomad4 NFE exome AF: 0.498

Gnomad4 OTH exome AF: 0.504

GnomAD4 genome AF: 0.489 AC: 73709 AN: 150740 Hom.: 18365 Cov.: 34 AF XY: 0.485 AC XY: 35668 AN XY: 73576

Gnomad4 AFR AF: 0.556

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.342

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.509

Alfa AF: 0.477 Hom.: 16409

Bravo AF: 0.487

Asia WGS AF: 0.374 AC: 1304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.2
Dann	Benign	0.61

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10111332; hg19: chr8-145747628;