12-69609715-G-A

Position:

• chr12-69609715-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_201550.4(LRRC10):​c.*290C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0646 in 418,330 control chromosomes in the GnomAD database, including 2,296 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.064 (611 hom., cov: 33)
  • Exomes 𝑓: 0.065 (1685 hom.)
• Consequence: LRRC10 NM_201550.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.136

Genes affected

LRRC10 (HGNC:20264): (leucine rich repeat containing 10) Predicted to enable actin binding activity. Predicted to be involved in cardiac muscle cell development. Predicted to be located in myofibril. Predicted to be active in cytoskeleton and sarcomere. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 12-69609715-G-A is Benign according to our data. Variant chr12-69609715-G-A is described in ClinVar as [Benign]. Clinvar id is 1182283.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC10	NM_201550.4	c.*290C>T		3_prime_UTR_variant	1/1	ENST00000361484.5	NP_963844.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC10	ENST00000361484.5	c.*290C>T		3_prime_UTR_variant	1/1		NM_201550.4	ENSP00000355166	P1

Frequencies

GnomAD3 genomes AF: 0.0641 AC: 9751 AN: 152076 Hom.: 610 Cov.: 33

Gnomad AFR AF: 0.0780

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0735

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.0580

Gnomad FIN AF: 0.0208

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0399

Gnomad OTH AF: 0.0587

GnomAD4 exome AF: 0.0648 AC: 17250 AN: 266136 Hom.: 1685 Cov.: 0 AF XY: 0.0636 AC XY: 8790 AN XY: 138104

Gnomad4 AFR exome AF: 0.0728

Gnomad4 AMR exome AF: 0.0905

Gnomad4 ASJ exome AF: 0.0254

Gnomad4 EAS exome AF: 0.388

Gnomad4 SAS exome AF: 0.0512

Gnomad4 FIN exome AF: 0.0254

Gnomad4 NFE exome AF: 0.0369

Gnomad4 OTH exome AF: 0.0581

GnomAD4 genome AF: 0.0641 AC: 9756 AN: 152194 Hom.: 611 Cov.: 33 AF XY: 0.0636 AC XY: 4731 AN XY: 74400

Gnomad4 AFR AF: 0.0781

Gnomad4 AMR AF: 0.0734

Gnomad4 ASJ AF: 0.0242

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.0576

Gnomad4 FIN AF: 0.0208

Gnomad4 NFE AF: 0.0399

Gnomad4 OTH AF: 0.0572

Alfa AF: 0.0464 Hom.: 233

Bravo AF: 0.0733

Asia WGS AF: 0.165 AC: 571 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.52

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: rs28204; hg19: chr12-70003495;