NM_014665.4:c.*766T>C

Variant names:

• chr8-144522244-T-C
• rs10111332
• NM_014665.4:c.*766T>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]

LRRC24 (HGNC:28947): (leucine rich repeat containing 24) Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be integral component of membrane. Predicted to be active in extracellular matrix and extracellular space. [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=-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 rank	MANE	Protein	UniProt
LRRC14	NM_014665.4	c.*766T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000292524.6	NP_055480.1
LRRC24	NM_001024678.4	c.*231A>G		downstream_gene_variant		ENST00000529415.7	NP_001019849.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC14	ENST00000292524.6	c.*766T>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_014665.4	ENSP00000292524.1
LRRC24	ENST00000529415.7	c.*231A>G		downstream_gene_variant		1	NM_001024678.4	ENSP00000434849.1
LRRC14	ENST00000529022.5	c.*766T>C		downstream_gene_variant		1		ENSP00000434768.1
LRRC24	ENST00000533758.1	c.*231A>G		downstream_gene_variant		5		ENSP00000435653.1

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;