rs7868184

Positions:

• chr9-124012236-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000373615.9(LHX2):​c.-113G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0628 in 1,117,780 control chromosomes in the GnomAD database, including 2,565 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 0.077 (561 hom., cov: 32)
  • Exomes 𝑓: 0.061 (2004 hom.)
• Consequence: LHX2 ENST00000373615.9 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.84

Genes affected

LHX2 (HGNC:6594): (LIM homeobox 2) This gene encodes a protein belonging to a large protein family, members of which carry the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein may function as a transcriptional regulator. The protein can recapitulate or rescue phenotypes in Drosophila caused by a related protein, suggesting conservation of function during evolution. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHX2	NM_004789.4	c.-113G>T		5_prime_UTR_variant	1/5	ENST00000373615.9	NP_004780.3
LHX2	XM_006717323.4	c.-113G>T		5_prime_UTR_variant	1/6		XP_006717386.1
LHX2	XM_047424082.1	c.-113G>T		5_prime_UTR_variant	1/6		XP_047280038.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHX2	ENST00000373615.9	c.-113G>T		5_prime_UTR_variant	1/5	1	NM_004789.4	ENSP00000362717	P1
LHX2	ENST00000560961.2	c.-3-1725G>T		intron_variant		3		ENSP00000453448

Frequencies

GnomAD3 genomes AF: 0.0768 AC: 11647 AN: 151584 Hom.: 562 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.0544

Gnomad ASJ AF: 0.0773

Gnomad EAS AF: 0.0280

Gnomad SAS AF: 0.0909

Gnomad FIN AF: 0.0432

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.0555

Gnomad OTH AF: 0.0716

GnomAD4 exome AF: 0.0606 AC: 58560 AN: 966086 Hom.: 2004 Cov.: 13 AF XY: 0.0613 AC XY: 28489 AN XY: 464514

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.0636

Gnomad4 ASJ exome AF: 0.0791

Gnomad4 EAS exome AF: 0.0256

Gnomad4 SAS exome AF: 0.0996

Gnomad4 FIN exome AF: 0.0570

Gnomad4 NFE exome AF: 0.0579

Gnomad4 OTH exome AF: 0.0649

GnomAD4 genome AF: 0.0768 AC: 11656 AN: 151694 Hom.: 561 Cov.: 32 AF XY: 0.0760 AC XY: 5638 AN XY: 74138

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0544

Gnomad4 ASJ AF: 0.0773

Gnomad4 EAS AF: 0.0281

Gnomad4 SAS AF: 0.0909

Gnomad4 FIN AF: 0.0432

Gnomad4 NFE AF: 0.0555

Gnomad4 OTH AF: 0.0709

Alfa AF: 0.0701 Hom.: 58

Bravo AF: 0.0798

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Benign	0.85

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: rs7868184; hg19: chr9-126774515;