8-144518144-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_014665.4(LRRC14):c.-112+103C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0093 in 161,572 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0097 (11 hom., cov: 34)
  • Exomes 𝑓: 0.0033 (0 hom.)
• Consequence: LRRC14 NM_014665.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.50

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 8-144518144-C-T is Benign according to our data. Variant chr8-144518144-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1187315.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00967 (1471/152068) while in subpopulation AFR AF= 0.0276 (1145/41494). AF 95% confidence interval is 0.0263. There are 11 homozygotes in gnomad4. There are 704 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC14	NM_014665.4	c.-112+103C>T		intron_variant		ENST00000292524.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC14	ENST00000292524.6	c.-112+103C>T		intron_variant		1	NM_014665.4	P1
LRRC14	ENST00000529022.5	c.-179+103C>T		intron_variant		1		P1
LRRC14	ENST00000527730.1	c.-26+103C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00956 AC: 1453 AN: 151960 Hom.: 9 Cov.: 34

Gnomad AFR AF: 0.0272

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00707

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.00231

Gnomad OTH AF: 0.0148

GnomAD4 exome AF: 0.00326 AC: 31 AN: 9504 Hom.: 0 AF XY: 0.00253 AC XY: 13 AN XY: 5138

Gnomad4 AFR exome AF: 0.0211

Gnomad4 AMR exome AF: 0.00379

Gnomad4 ASJ exome AF: 0.00658

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00234

Gnomad4 OTH exome AF: 0.00621

GnomAD4 genome AF: 0.00967 AC: 1471 AN: 152068 Hom.: 11 Cov.: 34 AF XY: 0.00947 AC XY: 704 AN XY: 74326

Gnomad4 AFR AF: 0.0276

Gnomad4 AMR AF: 0.00706

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000378

Gnomad4 NFE AF: 0.00231

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00656 Hom.: 1

Bravo AF: 0.0110

Asia WGS AF: 0.00261 AC: 9 AN: 3466

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 24, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	3.6
Dann	Benign	0.72
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.8

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: rs35791462; hg19: chr8-145743528;