NM_001193483.3:c.32+49606T>C

Variant names:

• chr2-108584200-T-C
• rs2577625
• NM_001193483.3:c.32+49606T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001193483.3(LIMS1):​c.32+49606T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 152,010 control chromosomes in the GnomAD database, including 30,351 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (30351 hom., cov: 31)
• Consequence: LIMS1 NM_001193483.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• Publications: 6 publications found

Genes affected

LIMS1 (HGNC:6616): (LIM zinc finger domain containing 1) The protein encoded by this gene is an adaptor protein which contains five LIM domains, or double zinc fingers. The protein is likely involved in integrin signaling through its LIM domain-mediated interaction with integrin-linked kinase, found in focal adhesion plaques. It is also thought to act as a bridge linking integrin-linked kinase to NCK adaptor protein 2, which is involved in growth factor receptor kinase signaling pathways. Its localization to the periphery of spreading cells also suggests that this protein may play a role in integrin-mediated cell adhesion or spreading. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193483.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIMS1	NM_001193483.3	MANE Select	c.32+49606T>C		intron	N/A	NP_001180412.1
	LIMS1	NM_001371495.1		c.32+49606T>C		intron	N/A	NP_001358424.1
	LIMS1	NM_001371496.1		c.59+50392T>C		intron	N/A	NP_001358425.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIMS1	ENST00000544547.6	TSL:1 MANE Select	c.32+49606T>C		intron	N/A	ENSP00000437912.1
	LIMS1	ENST00000695517.1		c.32+49606T>C		intron	N/A	ENSP00000511980.1
	LIMS1	ENST00000695516.1		c.59+50392T>C		intron	N/A	ENSP00000511979.1

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95036 AN: 151892 Hom.: 30319 Cov.: 31

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.614

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.626 AC: 95115 AN: 152010 Hom.: 30351 Cov.: 31 AF XY: 0.632 AC XY: 46932 AN XY: 74292

African (AFR) AF: 0.598 AC: 24794 AN: 41446

American (AMR) AF: 0.666 AC: 10177 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 1935 AN: 3472

East Asian (EAS) AF: 0.973 AC: 5013 AN: 5154

South Asian (SAS) AF: 0.602 AC: 2901 AN: 4822

European-Finnish (FIN) AF: 0.713 AC: 7533 AN: 10570

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.600 AC: 40769 AN: 67948

Other (OTH) AF: 0.616 AC: 1303 AN: 2114

Alfa AF: 0.599 Hom.: 13105

Bravo AF: 0.629

Asia WGS AF: 0.773 AC: 2687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.14
DANN	Benign	0.45
PhyloP100		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2577625; hg19: chr2-109200656;