Variant 17-36940617-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_005568.5(LHX1):c.405G>A(p.Thr135Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,613,760 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0099 ( 28 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 19 hom. )

Consequence

LHX1
NM_005568.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.606

Variant links:

Genes affected

LHX1 (HGNC:6593): (LIM homeobox 1) This gene encodes a member of a large protein family which contains the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein is a transcription factor important for the development of the renal and urogenital systems. This gene is a candidate for Mayer-Rokitansky-Kuster-Hauser syndrome, a disorder characterized by anomalies in the female genital tract. [provided by RefSeq, Dec 2010]

LHX1 links:

LHX1 (HGNC:):

LHX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 17-36940617-G-A is Benign according to our data. Variant chr17-36940617-G-A is described in ClinVar as [Benign]. Clinvar id is 3038454.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0099 (1508/152256) while in subpopulation AFR AF= 0.0342 (1423/41556). AF 95% confidence interval is 0.0328. There are 28 homozygotes in gnomad4. There are 688 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1508 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHX1	NM_005568.5 linkuse as main transcript	c.405G>A	p.Thr135Thr	synonymous_variant	3/5	ENST00000614239.1	NP_005559.2	P48742Q58F18
LHX1	XM_047435966.1 linkuse as main transcript	c.405G>A	p.Thr135Thr	synonymous_variant	4/6		XP_047291922.1
LHX1	XM_047435967.1 linkuse as main transcript	c.405G>A	p.Thr135Thr	synonymous_variant	4/6		XP_047291923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LHX1	ENST00000614239.1 linkuse as main transcript	c.405G>A	p.Thr135Thr	synonymous_variant	3/5	1	NM_005568.5	ENSP00000477829.1	P48742
LHX1	ENST00000616237.1 linkuse as main transcript	n.587G>A		non_coding_transcript_exon_variant	3/3	1
ENSG00000276707	ENST00000614759.1 linkuse as main transcript	n.368-392C>T		intron_variant		5
LHX1	ENST00000619939.4 linkuse as main transcript	n.961-35G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00989

AC:

1505

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0343

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00251

AC:

629

AN:

250990

Hom.:

AF XY:

0.00186

AC XY:

253

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.0324

Gnomad AMR exome

AF:

0.00205

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00106

AC:

1554

AN:

1461504

Hom.:

Cov.:

AF XY:

0.000919

AC XY:

668

AN XY:

727066

show subpopulations

Gnomad4 AFR exome

AF:

0.0350

Gnomad4 AMR exome

AF:

0.00230

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.0000692

Gnomad4 OTH exome

AF:

0.00282

GnomAD4 genome

AF:

0.00990

AC:

1508

AN:

152256

Hom.:

Cov.:

AF XY:

0.00924

AC XY:

688

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0342

Gnomad4 AMR

AF:

0.00373

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00497

Hom.:

Bravo

AF:

0.0109

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

LHX1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

5.6

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.51

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.51

Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over