4-41637499-A-G

Variant names:

• chr4-41637499-A-G
• rs4345220
• NM_001330672.2:c.2091-1433A>G

Variant summary

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

The NM_001330672.2(LIMCH1):​c.2091-1433A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 152,028 control chromosomes in the GnomAD database, including 20,504 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 0.52 (20504 hom., cov: 33)
• Consequence: LIMCH1 NM_001330672.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.346
• Publications: 5 publications found

Genes affected

LIMCH1 (HGNC:29191): (LIM and calponin homology domains 1) Enables myosin II head/neck binding activity. Involved in several processes, including cytoplasmic actin-based contraction involved in cell motility; positive regulation of stress fiber assembly; and regulation of focal adhesion assembly. Located in stress fiber. Colocalizes with myosin II complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330672.2. 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
	LIMCH1	NM_001330672.2	MANE Select	c.2091-1433A>G		intron	N/A	NP_001317601.1
	LIMCH1	NM_001330787.2		c.936-1433A>G		intron	N/A	NP_001317716.1
	LIMCH1	NM_014988.5		c.936-1433A>G		intron	N/A	NP_055803.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIMCH1	ENST00000503057.6	TSL:1 MANE Select	c.2091-1433A>G		intron	N/A	ENSP00000425631.1
	LIMCH1	ENST00000313860.12	TSL:1	c.936-1433A>G		intron	N/A	ENSP00000316891.7
	LIMCH1	ENST00000512820.5	TSL:1	c.936-7001A>G		intron	N/A	ENSP00000424437.1

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78351 AN: 151908 Hom.: 20474 Cov.: 33

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.516 AC: 78421 AN: 152028 Hom.: 20504 Cov.: 33 AF XY: 0.519 AC XY: 38581 AN XY: 74286

African (AFR) AF: 0.500 AC: 20755 AN: 41474

American (AMR) AF: 0.527 AC: 8051 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1612 AN: 3470

East Asian (EAS) AF: 0.193 AC: 996 AN: 5172

South Asian (SAS) AF: 0.538 AC: 2591 AN: 4820

European-Finnish (FIN) AF: 0.607 AC: 6404 AN: 10542

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.534 AC: 36309 AN: 67968

Other (OTH) AF: 0.479 AC: 1011 AN: 2112

Alfa AF: 0.515 Hom.: 60658

Bravo AF: 0.505

Asia WGS AF: 0.374 AC: 1304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.90
DANN	Benign	0.71
PhyloP100		-0.35
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: rs4345220; hg19: chr4-41639516;