8-144519798-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_014665.4(LRRC14):c.73T>C(p.Leu25=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.989 in 1,613,306 control chromosomes in the GnomAD database, including 790,801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.99 (74288 hom., cov: 36)
  • Exomes 𝑓: 0.99 (716513 hom.)
• Consequence: LRRC14 NM_014665.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.222

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 8-144519798-T-C is Benign according to our data. Variant chr8-144519798-T-C is described in ClinVar as [Benign]. Clinvar id is 403369.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.222 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC14	NM_014665.4	c.73T>C	p.Leu25=	synonymous_variant	2/4	ENST00000292524.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC14	ENST00000292524.6	c.73T>C	p.Leu25=	synonymous_variant	2/4	1	NM_014665.4	P1

Frequencies

GnomAD3 genomes AF: 0.987 AC: 150218 AN: 152246 Hom.: 74231 Cov.: 36

Gnomad AFR AF: 0.997

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.951

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.996

Gnomad FIN AF: 0.998

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.989

GnomAD3 exomes AF: 0.970 AC: 242698 AN: 250128 Hom.: 118201 AF XY: 0.976 AC XY: 132336 AN XY: 135654

Gnomad AFR exome AF: 0.998

Gnomad AMR exome AF: 0.902

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 0.796

Gnomad SAS exome AF: 0.998

Gnomad FIN exome AF: 0.997

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.982

GnomAD4 exome AF: 0.989 AC: 1445313 AN: 1460942 Hom.: 716513 Cov.: 78 AF XY: 0.990 AC XY: 719452 AN XY: 726770

Gnomad4 AFR exome AF: 0.998

Gnomad4 AMR exome AF: 0.908

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.744

Gnomad4 SAS exome AF: 0.999

Gnomad4 FIN exome AF: 0.996

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.989

GnomAD4 genome AF: 0.987 AC: 150334 AN: 152364 Hom.: 74288 Cov.: 36 AF XY: 0.985 AC XY: 73385 AN XY: 74500

Gnomad4 AFR AF: 0.997

Gnomad4 AMR AF: 0.951

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 0.795

Gnomad4 SAS AF: 0.997

Gnomad4 FIN AF: 0.998

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.989

Alfa AF: 0.997 Hom.: 37541

Bravo AF: 0.982

Asia WGS AF: 0.943 AC: 3280 AN: 3478

EpiCase AF: 1.00

EpiControl AF: 1.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	6.8
Dann	Benign	0.78

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: rs2721172; hg19: chr8-145745182; COSMIC: COSV52881411; COSMIC: COSV52881411;