rs148566929

chr12-69610071-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_201550.4(LRRC10):c.768G>A(p.Ala256=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000227 in 1,614,220 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00056 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00019 (1 hom.)
• Consequence: LRRC10 NM_201550.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.21

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 12-69610071-C-T is Benign according to our data. Variant chr12-69610071-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 478145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.21 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC10	NM_201550.4	c.768G>A	p.Ala256=	synonymous_variant	1/1	ENST00000361484.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC10	ENST00000361484.5	c.768G>A	p.Ala256=	synonymous_variant	1/1		NM_201550.4	P1

Frequencies

GnomAD3 genomes AF: 0.000558 AC: 85 AN: 152210 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000243 AC: 61 AN: 251448 Hom.: 1 AF XY: 0.000272 AC XY: 37 AN XY: 135898

Gnomad AFR exome AF: 0.00191

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.000893

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000192 AC: 281 AN: 1461892 Hom.: 1 Cov.: 31 AF XY: 0.000194 AC XY: 141 AN XY: 727248

Gnomad4 AFR exome AF: 0.00293

Gnomad4 AMR exome AF: 0.0000894

Gnomad4 ASJ exome AF: 0.00119

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000576

Gnomad4 OTH exome AF: 0.000960

GnomAD4 genome AF: 0.000565 AC: 86 AN: 152328 Hom.: 1 Cov.: 33 AF XY: 0.000631 AC XY: 47 AN XY: 74488

Gnomad4 AFR AF: 0.00171

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000540 Hom.: 0

Bravo AF: 0.000638

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000296

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Dilated Cardiomyopathy, Dominant Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 18, 2024

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 27, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	0.44
Dann	Benign	0.48

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: rs148566929; hg19: chr12-70003851;