rs1377347

Variant names:

• chr4-41370585-T-G
• rs1377347
• ENST00000313860.12:c.96+9649T>G

Variant summary

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

The ENST00000313860.12(LIMCH1):​c.96+9649T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,914 control chromosomes in the GnomAD database, including 14,831 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 0.42 (14831 hom., cov: 32)
• Consequence: LIMCH1 ENST00000313860.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.429
• Publications: 3 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=-0.6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIMCH1	NM_001330787.2	c.96+9649T>G		intron_variant	Intron 1 of 26		NP_001317716.1
LIMCH1	NM_014988.5	c.96+9649T>G		intron_variant	Intron 1 of 26		NP_055803.2
LIMCH1	NM_001330790.2	c.96+9649T>G		intron_variant	Intron 1 of 26		NP_001317719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIMCH1	ENST00000313860.12	c.96+9649T>G		intron_variant	Intron 1 of 26	1		ENSP00000316891.7
LIMCH1	ENST00000512820.5	c.96+9649T>G		intron_variant	Intron 1 of 25	1		ENSP00000424437.1
LIMCH1	ENST00000512946.5	c.96+9649T>G		intron_variant	Intron 1 of 25	1		ENSP00000424645.1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63449 AN: 151796 Hom.: 14810 Cov.: 32

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.394

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

GnomAD4 genome AF: 0.418 AC: 63520 AN: 151914 Hom.: 14831 Cov.: 32 AF XY: 0.419 AC XY: 31121 AN XY: 74228

African (AFR) AF: 0.640 AC: 26486 AN: 41388

American (AMR) AF: 0.417 AC: 6368 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1703 AN: 3468

East Asian (EAS) AF: 0.393 AC: 2020 AN: 5146

South Asian (SAS) AF: 0.436 AC: 2092 AN: 4800

European-Finnish (FIN) AF: 0.322 AC: 3407 AN: 10568

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20312 AN: 67970

Other (OTH) AF: 0.390 AC: 819 AN: 2102

Alfa AF: 0.344 Hom.: 5172

Bravo AF: 0.431

Asia WGS AF: 0.418 AC: 1458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	10
DANN	Benign	0.83
PhyloP100		0.43
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: rs1377347; hg19: chr4-41372602;