10-101227402-G-C

Position:

• chr10-101227402-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_006562.5(LBX1):​c.714C>G​(p.Pro238=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,601,648 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0082 (23 hom., cov: 33)
  • Exomes 𝑓: 0.00098 (19 hom.)
• Consequence: LBX1 NM_006562.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0980

Genes affected

LBX1 (HGNC:16960): (ladybird homeobox 1) This gene and the orthologous mouse gene were found by their homology to the Drosophila lady bird early and late homeobox genes. In the mouse, this gene is a key regulator of muscle precursor cell migration and is required for the acquisition of dorsal identities of forelimb muscles. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 10-101227402-G-C is Benign according to our data. Variant chr10-101227402-G-C is described in ClinVar as [Benign]. Clinvar id is 780888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.098 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00821 (1251/152334) while in subpopulation AFR AF= 0.028 (1166/41580). AF 95% confidence interval is 0.0267. There are 23 homozygotes in gnomad4. There are 624 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LBX1	NM_006562.5	c.714C>G	p.Pro238=	synonymous_variant	2/2	ENST00000370193.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LBX1	ENST00000370193.4	c.714C>G	p.Pro238=	synonymous_variant	2/2	1	NM_006562.5	P1

Frequencies

GnomAD3 genomes AF: 0.00821 AC: 1250 AN: 152218 Hom.: 23 Cov.: 33

Gnomad AFR AF: 0.0281

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00334

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00211 AC: 467 AN: 221654 Hom.: 4 AF XY: 0.00175 AC XY: 216 AN XY: 123246

Gnomad AFR exome AF: 0.0265

Gnomad AMR exome AF: 0.00203

Gnomad ASJ exome AF: 0.00184

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000337

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000282

Gnomad OTH exome AF: 0.00254

GnomAD4 exome AF: 0.000984 AC: 1426 AN: 1449314 Hom.: 19 Cov.: 31 AF XY: 0.000806 AC XY: 581 AN XY: 720674

Gnomad4 AFR exome AF: 0.0291

Gnomad4 AMR exome AF: 0.00233

Gnomad4 ASJ exome AF: 0.00132

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000234

Gnomad4 FIN exome AF: 0.0000614

Gnomad4 NFE exome AF: 0.000207

Gnomad4 OTH exome AF: 0.00154

GnomAD4 genome AF: 0.00821 AC: 1251 AN: 152334 Hom.: 23 Cov.: 33 AF XY: 0.00838 AC XY: 624 AN XY: 74492

Gnomad4 AFR AF: 0.0280

Gnomad4 AMR AF: 0.00333

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00111 Hom.: 0

Bravo AF: 0.00911

Asia WGS AF: 0.000289 AC: 1 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	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	2.2
DANN	Benign	0.76

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: rs200155323; hg19: chr10-102987159;