8-144525122-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014665.4(LRRC14):​c.*3644G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 793,018 control chromosomes in the GnomAD database, including 96,068 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 0.54 (22648 hom., cov: 35)
  • Exomes 𝑓: 0.47 (73420 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.643 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.*3644G>A		3_prime_UTR	Exon 4 of 4	NP_055480.1	Q15048
	LRRC24	NM_001024678.4	MANE Select	c.-59-89C>T		intron	N/A	NP_001019849.2	Q50LG9
	LRRC14	NM_001272036.2		c.*3644G>A		3_prime_UTR	Exon 5 of 5	NP_001258965.1	Q15048

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC14	ENST00000292524.6	TSL:1 MANE Select	c.*3644G>A		3_prime_UTR	Exon 4 of 4	ENSP00000292524.1	Q15048
	LRRC24	ENST00000529415.7	TSL:1 MANE Select	c.-59-89C>T		intron	N/A	ENSP00000434849.1	Q50LG9
	LRRC14	ENST00000887351.1		c.*3644G>A		3_prime_UTR	Exon 5 of 5	ENSP00000557410.1

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81940 AN: 152100 Hom.: 22614 Cov.: 35

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.535

GnomAD4 exome AF: 0.473 AC: 303029 AN: 640800 Hom.: 73420 Cov.: 9 AF XY: 0.476 AC XY: 150469 AN XY: 316250

African (AFR) AF: 0.637 AC: 8495 AN: 13330

American (AMR) AF: 0.561 AC: 5756 AN: 10266

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 5999 AN: 12556

East Asian (EAS) AF: 0.410 AC: 10416 AN: 25374

South Asian (SAS) AF: 0.572 AC: 14159 AN: 24736

European-Finnish (FIN) AF: 0.495 AC: 12696 AN: 25654

Middle Eastern (MID) AF: 0.419 AC: 922 AN: 2200

European-Non Finnish (NFE) AF: 0.463 AC: 229857 AN: 496452

Other (OTH) AF: 0.487 AC: 14729 AN: 30232

GnomAD4 genome AF: 0.539 AC: 82024 AN: 152218 Hom.: 22648 Cov.: 35 AF XY: 0.543 AC XY: 40382 AN XY: 74426

African (AFR) AF: 0.649 AC: 26966 AN: 41540

American (AMR) AF: 0.567 AC: 8669 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1664 AN: 3470

East Asian (EAS) AF: 0.480 AC: 2486 AN: 5180

South Asian (SAS) AF: 0.588 AC: 2839 AN: 4830

European-Finnish (FIN) AF: 0.501 AC: 5308 AN: 10600

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.479 AC: 32583 AN: 67992

Other (OTH) AF: 0.534 AC: 1126 AN: 2110

Alfa AF: 0.501 Hom.: 59487

Bravo AF: 0.547

Asia WGS AF: 0.578 AC: 2009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.3
DANN	Benign	0.67
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9071; hg19: chr8-145750506;