chr14-68941980-G-A

Variant names:

• chr14-68941980-G-A
• rs2268983
• NM_001130004.2:c.106-16308C>T

Variant summary

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

The NM_001130004.2(ACTN1):​c.106-16308C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 151,990 control chromosomes in the GnomAD database, including 31,236 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 (31236 hom., cov: 31)
• Consequence: ACTN1 NM_001130004.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.181
• Publications: 13 publications found

Genes affected

ACTN1 (HGNC:163): (actinin alpha 1) 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 nonmuscle, cytoskeletal, alpha actinin isoform and maps to the same site as the structurally similar erythroid beta spectrin gene. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACTN1 Gene-Disease associations (from GenCC):

• platelet-type bleeding disorder 15

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• autosomal dominant macrothrombocytopenia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130004.2. 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
	ACTN1	NM_001130004.2	MANE Select	c.106-16308C>T		intron	N/A	NP_001123476.1
	ACTN1	NM_001424012.1		c.106-16308C>T		intron	N/A	NP_001410941.1
	ACTN1	NM_001424013.1		c.106-16308C>T		intron	N/A	NP_001410942.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTN1	ENST00000394419.9	TSL:1 MANE Select	c.106-16308C>T		intron	N/A	ENSP00000377941.4
	ACTN1	ENST00000538545.6	TSL:1	c.106-16308C>T		intron	N/A	ENSP00000439828.2
	ACTN1	ENST00000193403.11	TSL:1	c.106-16308C>T		intron	N/A	ENSP00000193403.6

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95254 AN: 151872 Hom.: 31181 Cov.: 31

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.628 AC: 95381 AN: 151990 Hom.: 31236 Cov.: 31 AF XY: 0.636 AC XY: 47197 AN XY: 74262

African (AFR) AF: 0.798 AC: 33088 AN: 41458

American (AMR) AF: 0.578 AC: 8835 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1423 AN: 3466

East Asian (EAS) AF: 0.780 AC: 4017 AN: 5150

South Asian (SAS) AF: 0.681 AC: 3275 AN: 4812

European-Finnish (FIN) AF: 0.681 AC: 7192 AN: 10560

Middle Eastern (MID) AF: 0.428 AC: 125 AN: 292

European-Non Finnish (NFE) AF: 0.526 AC: 35711 AN: 67950

Other (OTH) AF: 0.576 AC: 1214 AN: 2106

Alfa AF: 0.547 Hom.: 106771

Bravo AF: 0.624

Asia WGS AF: 0.738 AC: 2569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.9
DANN	Benign	0.51
PhyloP100		-0.18
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: rs2268983; hg19: chr14-69408697;