chr8-144525122-G-C

Variant names:

• chr8-144525122-G-C
• rs9071
• NM_014665.4:c.*3644G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014665.4(LRRC14):​c.*3644G>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 0.00000156 in 642,938 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 35)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: LRRC14 NM_014665.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275
• Publications: 25 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]

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC14	NM_014665.4	MANE Select	c.*3644G>C		3_prime_UTR	Exon 4 of 4	NP_055480.1
	LRRC24	NM_001024678.4	MANE Select	c.-59-89C>G		intron	N/A	NP_001019849.2
	LRRC14	NM_001272036.2		c.*3644G>C		3_prime_UTR	Exon 5 of 5	NP_001258965.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC14	ENST00000292524.6	TSL:1 MANE Select	c.*3644G>C		3_prime_UTR	Exon 4 of 4	ENSP00000292524.1
	LRRC24	ENST00000529415.7	TSL:1 MANE Select	c.-59-89C>G		intron	N/A	ENSP00000434849.1
	LRRC24	ENST00000533758.1	TSL:5	c.-59-89C>G		intron	N/A	ENSP00000435653.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 0.00000156 AC: 1 AN: 642938 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 317312

African (AFR) AF: 0.00 AC: 0 AN: 13352

American (AMR) AF: 0.00 AC: 0 AN: 10288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12580

East Asian (EAS) AF: 0.00 AC: 0 AN: 25384

South Asian (SAS) AF: 0.00 AC: 0 AN: 24816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25680

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2208

European-Non Finnish (NFE) AF: 0.00000201 AC: 1 AN: 498322

Other (OTH) AF: 0.00 AC: 0 AN: 30308

GnomAD4 genome Cov.: 35

Alfa AF: 0.00 Hom.: 59487

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.48
PhyloP100		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.36		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.36		Position offset: 0

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

Other links and lift over

dbSNP: rs9071; hg19: chr8-145750506;