17-36940278-AC-A

Position:

• chr17-36940278-AC-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_005568.5(LHX1):​c.171-5delC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 291,844 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0013 (0 hom.)
• Consequence: LHX1 NM_005568.5 splice_region, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0170

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 17-36940278-AC-A is Benign according to our data. Variant chr17-36940278-AC-A is described in ClinVar as [Likely_benign]. Clinvar id is 3044599.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 73 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LHX1	NM_005568.5	c.171-5delC		splice_region_variant, intron_variant		ENST00000614239.1	NP_005559.2
LHX1	XM_047435966.1	c.171-5delC		splice_region_variant, intron_variant			XP_047291922.1
LHX1	XM_047435967.1	c.171-5delC		splice_region_variant, intron_variant			XP_047291923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LHX1	ENST00000614239.1	c.171-5delC		splice_region_variant, intron_variant		1	NM_005568.5	ENSP00000477829.1

Frequencies

GnomAD3 genomes AF: 0.00145 AC: 73 AN: 50498 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000523

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000650

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000319

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00239

Gnomad OTH AF: 0.00698

GnomAD4 exome AF: 0.00131 AC: 315 AN: 241346 Hom.: 0 Cov.: 15 AF XY: 0.00115 AC XY: 151 AN XY: 131390

Gnomad4 AFR exome AF: 0.000381

Gnomad4 AMR exome AF: 0.000813

Gnomad4 ASJ exome AF: 0.000117

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000701

Gnomad4 NFE exome AF: 0.00209

Gnomad4 OTH exome AF: 0.00125

GnomAD4 genome AF: 0.00145 AC: 73 AN: 50498 Hom.: 0 Cov.: 30 AF XY: 0.00133 AC XY: 32 AN XY: 24134

Gnomad4 AFR AF: 0.000523

Gnomad4 AMR AF: 0.000650

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000319

Gnomad4 NFE AF: 0.00239

Gnomad4 OTH AF: 0.00698

Alfa AF: 0.0000713 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

LHX1-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 25, 2019

This variant is classified as likely 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

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: rs749643400; hg19: chr17-35297575;