rs1467737

Positions:

• chr9-122220221-C-T

Variant summary

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

The NM_014368.5(LHX6):​c.462-2933G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 152,152 control chromosomes in the GnomAD database, including 15,348 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 0.44 (15348 hom., cov: 33)
• Consequence: LHX6 NM_014368.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.600

Genes affected

LHX6 (HGNC:21735): (LIM homeobox 6) This gene encodes a member of a large protein family that contains the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein has tandem LIM domains as well as a DNA-binding homeodomain. The protein functions as a transcription factor involved in embryogenesis and head development and is highly expressed in neural crest derived mesenchyme cells. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LHX6	NM_014368.5	c.462-2933G>A		intron_variant		ENST00000394319.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LHX6	ENST00000394319.9	c.462-2933G>A		intron_variant		1	NM_014368.5	P1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66613 AN: 152034 Hom.: 15324 Cov.: 33

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.440

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.438 AC: 66675 AN: 152152 Hom.: 15348 Cov.: 33 AF XY: 0.445 AC XY: 33101 AN XY: 74386

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.529

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.478

Gnomad4 OTH AF: 0.444

Alfa AF: 0.474 Hom.: 14569

Bravo AF: 0.441

Asia WGS AF: 0.488 AC: 1697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.3
DANN	Benign	0.84

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: rs1467737; hg19: chr9-124982500;