rs6703000

Variant names:

• chr1-165210637-C-A
• rs6703000
• NM_177398.4:c.747+62G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_177398.4(LMX1A):​c.747+62G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.031 in 1,265,156 control chromosomes in the GnomAD database, including 3,036 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.091 (1678 hom., cov: 33)
  • Exomes 𝑓: 0.023 (1358 hom.)
• Consequence: LMX1A NM_177398.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0600
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-165210637-C-A is Benign according to our data. Variant chr1-165210637-C-A is described in ClinVar as [Benign]. Clinvar id is 1244331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMX1A	NM_177398.4	c.747+62G>T		intron_variant	Intron 6 of 8	ENST00000342310.7	NP_796372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMX1A	ENST00000342310.7	c.747+62G>T		intron_variant	Intron 6 of 8	2	NM_177398.4	ENSP00000340226.3

Frequencies

GnomAD3 genomes AF: 0.0905 AC: 13762 AN: 152034 Hom.: 1674 Cov.: 33

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.0541

Gnomad ASJ AF: 0.0352

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.00560

Gnomad FIN AF: 0.0139

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0155

Gnomad OTH AF: 0.0819

GnomAD4 exome AF: 0.0228 AC: 25404 AN: 1113004 Hom.: 1358 Cov.: 14 AF XY: 0.0215 AC XY: 12208 AN XY: 567988

African (AFR) AF: 0.287 AC: 7671 AN: 26684

American (AMR) AF: 0.0367 AC: 1571 AN: 42804

Ashkenazi Jewish (ASJ) AF: 0.0402 AC: 939 AN: 23332

East Asian (EAS) AF: 0.0000265 AC: 1 AN: 37678

South Asian (SAS) AF: 0.00587 AC: 449 AN: 76504

European-Finnish (FIN) AF: 0.0127 AC: 670 AN: 52720

Middle Eastern (MID) AF: 0.109 AC: 560 AN: 5126

European-Non Finnish (NFE) AF: 0.0145 AC: 11624 AN: 799554

Other (OTH) AF: 0.0395 AC: 1919 AN: 48602

GnomAD4 genome AF: 0.0906 AC: 13780 AN: 152152 Hom.: 1678 Cov.: 33 AF XY: 0.0877 AC XY: 6521 AN XY: 74378

African (AFR) AF: 0.275 AC: 11385 AN: 41464

American (AMR) AF: 0.0539 AC: 825 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0352 AC: 122 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.00477 AC: 23 AN: 4820

European-Finnish (FIN) AF: 0.0139 AC: 147 AN: 10602

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0154 AC: 1049 AN: 68000

Other (OTH) AF: 0.0810 AC: 171 AN: 2110

Alfa AF: 0.0392 Hom.: 740

Bravo AF: 0.104

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 14, 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	-0.80
CADD	Benign	2.3
DANN	Benign	0.47
PhyloP100		0.060
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: rs6703000; hg19: chr1-165179874;