rs187240783

Variant names:

• chr1-165210694-G-A
• rs187240783
• NM_177398.4:c.747+5C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-165210694-G-A
• chr1-165210694-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_177398.4(LMX1A):​c.747+5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000808 in 1,609,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000066 (0 hom.)
• Consequence: LMX1A NM_177398.4 splice_region, intron
• Scores: Splicing: ADA: 0.004177
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.950
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-165210694-G-A is Benign according to our data. Variant chr1-165210694-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3024964.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000223 (34/152310) while in subpopulation AMR AF = 0.00163 (25/15304). AF 95% confidence interval is 0.00113. There are 0 homozygotes in GnomAd4. There are 24 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177398.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMX1A	NM_177398.4	MANE Select	c.747+5C>T		splice_region intron	N/A	NP_796372.1	Q8TE12-1
	LMX1A	NM_001174069.2		c.747+5C>T		splice_region intron	N/A	NP_001167540.1	Q8TE12-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMX1A	ENST00000342310.7	TSL:2 MANE Select	c.747+5C>T		splice_region intron	N/A	ENSP00000340226.3	Q8TE12-1
	LMX1A	ENST00000367893.4	TSL:1	c.747+5C>T		splice_region intron	N/A	ENSP00000356868.4	Q8TE12-1
	LMX1A	ENST00000489443.2	TSL:1	n.248+5C>T		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000223 AC: 34 AN: 152192 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000175 AC: 44 AN: 251002 AF XY: 0.000162

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000659 AC: 96 AN: 1456736 Hom.: 0 Cov.: 29 AF XY: 0.0000731 AC XY: 53 AN XY: 725078

African (AFR) AF: 0.00 AC: 0 AN: 33378

American (AMR) AF: 0.00125 AC: 56 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 86020

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000208 AC: 23 AN: 1107550

Other (OTH) AF: 0.000199 AC: 12 AN: 60202

GnomAD4 genome AF: 0.000223 AC: 34 AN: 152310 Hom.: 0 Cov.: 33 AF XY: 0.000322 AC XY: 24 AN XY: 74462

African (AFR) AF: 0.0000241 AC: 1 AN: 41558

American (AMR) AF: 0.00163 AC: 25 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68026

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.0000993 Hom.: 0

Bravo AF: 0.000298

EpiCase AF: 0.0000547

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	LMX1A-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.7
DANN	Benign	0.76
PhyloP100		-0.95

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0042
dbscSNV1_RF	Benign	0.090
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: rs187240783; hg19: chr1-165179931;