dbSNP rs989798: LHX6:c.1055-46G>A (chr9-122209763-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0330

Publications

8 publications found

Variant links:

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]

LHX6 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

LHX6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LHX6	NM_014368.5 link	c.1055-46G>A		intron_variant	Intron 8 of 9	ENST00000394319.9	NP_055183.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LHX6	ENST00000394319.9 link	c.1055-46G>A		intron_variant	Intron 8 of 9	1	NM_014368.5	ENSP00000377854.4		Q9UPM6-3

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41680

AN:

151970

Hom.:

6065

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.283

AC:

57747

AN:

203740

AF XY:

0.282

show subpopulations

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 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.:

AF XY:

0.287

AC XY:

91969

AN XY:

320746

show subpopulations

African (AFR)

AF:

0.196

AC:

3403

AN:

17336

American (AMR)

AF:

0.209

AC:

8565

AN:

41020

Ashkenazi Jewish (ASJ)

AF:

0.343

AC:

6325

AN:

18448

East Asian (EAS)

AF:

0.253

AC:

8991

AN:

35474

South Asian (SAS)

AF:

0.133

AC:

8333

AN:

62592

European-Finnish (FIN)

AF:

0.356

AC:

16992

AN:

47762

Middle Eastern (MID)

AF:

0.358

AC:

1411

AN:

3944

European-Non Finnish (NFE)

AF:

0.328

AC:

110001

AN:

335090

Other (OTH)

AF:

0.306

AC:

9682

AN:

31670

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

6340

12680

19020

25360

31700

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

656

1312

1968

2624

3280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.274

AC:

41674

AN:

152088

Hom.:

6065

Cov.:

AF XY:

0.270

AC XY:

20034

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.196

AC:

8139

AN:

41518

American (AMR)

AF:

0.231

AC:

3528

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.340

AC:

1179

AN:

3468

East Asian (EAS)

AF:

0.299

AC:

1543

AN:

5156

South Asian (SAS)

AF:

0.129

AC:

623

AN:

4826

European-Finnish (FIN)

AF:

0.345

AC:

3651

AN:

10570

Middle Eastern (MID)

AF:

0.354

AC:

104

AN:

294

European-Non Finnish (NFE)

AF:

0.327

AC:

22218

AN:

67950

Other (OTH)

AF:

0.268

AC:

567

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1534

3068

4603

6137

7671

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

418

836

1254

1672

2090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.74

PhyloP100

-0.033

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over