rs989798

chr9-122209763-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.1055-46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 745,424 control chromosomes in the GnomAD database, including 33,098 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 0.27 (6065 hom., cov: 32)
  • Exomes 𝑓: 0.29 (27033 hom.)
• Consequence: LHX6 NM_014368.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LHX6	NM_014368.5	c.1055-46G>A		intron_variant		ENST00000394319.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LHX6	ENST00000394319.9	c.1055-46G>A		intron_variant		1	NM_014368.5	P1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41680 AN: 151970 Hom.: 6065 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.270

GnomAD3 exomes AF: 0.283 AC: 57747 AN: 203740 Hom.: 8639 AF XY: 0.282 AC XY: 30747 AN XY: 108912

Gnomad AFR exome AF: 0.200

Gnomad AMR exome AF: 0.207

Gnomad ASJ exome AF: 0.344

Gnomad EAS exome AF: 0.319

Gnomad SAS exome AF: 0.131

Gnomad FIN exome AF: 0.361

Gnomad NFE exome AF: 0.334

Gnomad OTH exome AF: 0.314

GnomAD4 exome AF: 0.293 AC: 173703 AN: 593336 Hom.: 27033 Cov.: 5 AF XY: 0.287 AC XY: 91969 AN XY: 320746

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.209

Gnomad4 ASJ exome AF: 0.343

Gnomad4 EAS exome AF: 0.253

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.356

Gnomad4 NFE exome AF: 0.328

Gnomad4 OTH exome AF: 0.306

GnomAD4 genome AF: 0.274 AC: 41674 AN: 152088 Hom.: 6065 Cov.: 32 AF XY: 0.270 AC XY: 20034 AN XY: 74320

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.268

Alfa AF: 0.310 Hom.: 1671

Bravo AF: 0.266

Asia WGS AF: 0.223 AC: 774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	7.8
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs989798; hg19: chr9-124972042;