rs2721173

Variant names:

• chr8-144519045-C-T
• rs2721173
• NM_014665.4:c.-111-570C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 31 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014665.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC14	NM_014665.4	MANE Select	c.-111-570C>T		intron	N/A	NP_055480.1
	LRRC14	NM_001272036.2		c.-112+230C>T		intron	N/A	NP_001258965.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC14	ENST00000292524.6	TSL:1 MANE Select	c.-111-570C>T		intron	N/A	ENSP00000292524.1
	LRRC14	ENST00000529022.5	TSL:1	c.-112+230C>T		intron	N/A	ENSP00000434768.1
	LRRC14	ENST00000927377.1		c.-681C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000597436.1

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

African (AFR) AF: 0.288 AC: 11965 AN: 41486

American (AMR) AF: 0.534 AC: 8151 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1645 AN: 3470

East Asian (EAS) AF: 0.477 AC: 2467 AN: 5170

South Asian (SAS) AF: 0.589 AC: 2843 AN: 4830

European-Finnish (FIN) AF: 0.502 AC: 5312 AN: 10574

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.478 AC: 32495 AN: 67988

Other (OTH) AF: 0.466 AC: 985 AN: 2114

Alfa AF: 0.460 Hom.: 9138

Bravo AF: 0.430

Asia WGS AF: 0.559 AC: 1943 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.65
DANN	Benign	0.52
PhyloP100		-1.4
PromoterAI		-0.058	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2721173; hg19: chr8-145744429;