1-165205722-C-T

Variant names:

• chr1-165205722-C-T
• rs16841013
• NM_177398.4:c.988+142G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_177398.4(LMX1A):​c.988+142G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 706,182 control chromosomes in the GnomAD database, including 25,746 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (4390 hom., cov: 32)
  • Exomes 𝑓: 0.26 (21356 hom.)
• Consequence: LMX1A NM_177398.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.370
• Publications: 3 publications found

Genes affected

LMX1A (HGNC:6653): (LIM homeobox transcription factor 1 alpha) This gene encodes a homeodomain and LIM-domain containing protein. The encoded protein is a transcription factor that acts as a positive regulator of insulin gene transcription. This gene also plays a role in the development of dopamine producing neurons during embryogenesis. Mutations in this gene are associated with an increased risk of developing Parkinson's disease. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

LMX1A-AS2 (HGNC:40343): (LMX1A antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-165205722-C-T is Benign according to our data. Variant chr1-165205722-C-T is described in ClinVar as [Benign]. Clinvar id is 1236257.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMX1A	NM_177398.4	c.988+142G>A		intron_variant	Intron 8 of 8	ENST00000342310.7	NP_796372.1
LMX1A-AS2	XR_922234.2	n.318C>T		non_coding_transcript_exon_variant	Exon 2 of 6
LMX1A	NM_001174069.2	c.988+142G>A		intron_variant	Intron 8 of 8		NP_001167540.1
LMX1A	XM_011509538.4	c.748+142G>A		intron_variant	Intron 6 of 6		XP_011507840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMX1A	ENST00000342310.7	c.988+142G>A		intron_variant	Intron 8 of 8	2	NM_177398.4	ENSP00000340226.3
LMX1A	ENST00000367893.4	c.988+142G>A		intron_variant	Intron 7 of 7	1		ENSP00000356868.4
LMX1A	ENST00000489443.2	n.622+142G>A		intron_variant	Intron 6 of 6	1
LMX1A	ENST00000294816.6	c.988+142G>A		intron_variant	Intron 8 of 8	2		ENSP00000294816.2

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32004 AN: 151996 Hom.: 4386 Cov.: 32

Gnomad AFR AF: 0.0609

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.262 AC: 145398 AN: 554068 Hom.: 21356 AF XY: 0.266 AC XY: 77688 AN XY: 292012

African (AFR) AF: 0.0584 AC: 804 AN: 13758

American (AMR) AF: 0.421 AC: 9775 AN: 23200

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 4414 AN: 14170

East Asian (EAS) AF: 0.471 AC: 14986 AN: 31810

South Asian (SAS) AF: 0.360 AC: 17153 AN: 47658

European-Finnish (FIN) AF: 0.258 AC: 11760 AN: 45578

Middle Eastern (MID) AF: 0.227 AC: 478 AN: 2106

European-Non Finnish (NFE) AF: 0.228 AC: 78906 AN: 346692

Other (OTH) AF: 0.245 AC: 7122 AN: 29096

GnomAD4 genome AF: 0.210 AC: 32019 AN: 152114 Hom.: 4390 Cov.: 32 AF XY: 0.220 AC XY: 16373 AN XY: 74346

African (AFR) AF: 0.0611 AC: 2536 AN: 41510

American (AMR) AF: 0.322 AC: 4917 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1146 AN: 3470

East Asian (EAS) AF: 0.487 AC: 2521 AN: 5178

South Asian (SAS) AF: 0.364 AC: 1755 AN: 4822

European-Finnish (FIN) AF: 0.273 AC: 2888 AN: 10572

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15664 AN: 67972

Other (OTH) AF: 0.218 AC: 459 AN: 2110

Alfa AF: 0.218 Hom.: 6237

Bravo AF: 0.208

Asia WGS AF: 0.382 AC: 1329 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.78
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16841013; hg19: chr1-165174959;