1-236686477-C-T

Variant names:

• chr1-236686477-C-T
• rs980228032
• ENST00000651187.1:c.-91+9367C>T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The ENST00000651187.1(ACTN2):​c.-91+9367C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000337 in 343,896 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00031 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00035 (0 hom.)
• Consequence: ACTN2 ENST00000651187.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.78

Genes affected

ACTN2 (HGNC:164): (actinin alpha 2) Alpha actinins belong to the spectrin gene superfamily which represents a diverse group of cytoskeletal proteins, including the alpha and beta spectrins and dystrophins. Alpha actinin is an actin-binding protein with multiple roles in different cell types. In nonmuscle cells, the cytoskeletal isoform is found along microfilament bundles and adherens-type junctions, where it is involved in binding actin to the membrane. In contrast, skeletal, cardiac, and smooth muscle isoforms are localized to the Z-disc and analogous dense bodies, where they help anchor the myofibrillar actin filaments. This gene encodes a muscle-specific, alpha actinin isoform that is expressed in both skeletal and cardiac muscles. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BS2: High AC in GnomAd4 at 47 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTN2	NM_001103.4	c.-197C>T		upstream_gene_variant		ENST00000366578.6	NP_001094.1
ACTN2	NM_001278343.2	c.-197C>T		upstream_gene_variant			NP_001265272.1
ACTN2	NR_184402.1	n.-22C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTN2	ENST00000366578.6	c.-197C>T		upstream_gene_variant		1	NM_001103.4	ENSP00000355537.4

Frequencies

GnomAD3 genomes AF: 0.000315 AC: 47 AN: 149442 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000487

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000507

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000355 AC: 69 AN: 194454 Hom.: 0 Cov.: 5 AF XY: 0.000266 AC XY: 26 AN XY: 97692

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000504

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000849

Gnomad4 NFE exome AF: 0.000366

Gnomad4 OTH exome AF: 0.000470

GnomAD4 genome AF: 0.000315 AC: 47 AN: 149442 Hom.: 0 Cov.: 31 AF XY: 0.000316 AC XY: 23 AN XY: 72870

Gnomad4 AFR AF: 0.0000487

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.000507

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000107 Hom.: 0

Bravo AF: 0.000215

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	4.2
DANN	Benign	0.97

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs980228032; hg19: chr1-236849777;