4-41637499-A-G

Position:

• chr4-41637499-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIMCH1	NM_001330672.2	c.2091-1433A>G		intron_variant		ENST00000503057.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIMCH1	ENST00000503057.6	c.2091-1433A>G		intron_variant		1	NM_001330672.2

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

Gnomad4 AFR AF: 0.500

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.479

Alfa AF: 0.513 Hom.: 25523

Bravo AF: 0.505

Asia WGS AF: 0.374 AC: 1304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.90
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs4345220; hg19: chr4-41639516;