NM_001130004.2:c.105+18C>T

Variant names:

• chr14-68978934-G-A
• rs185589644
• NM_001130004.2:c.105+18C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001130004.2(ACTN1):​c.105+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00387 in 1,546,722 control chromosomes in the GnomAD database, including 222 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (111 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (111 hom.)
• Consequence: ACTN1 NM_001130004.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.78
• Publications: 0 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-DT (HGNC:20131): (ACTN1 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 14-68978934-G-A is Benign according to our data. Variant chr14-68978934-G-A is described in ClinVar as Benign. ClinVar VariationId is 1268737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0688 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTN1	NM_001130004.2	MANE Select	c.105+18C>T		intron	N/A	NP_001123476.1	P12814-3
	ACTN1	NM_001424012.1		c.105+18C>T		intron	N/A	NP_001410941.1
	ACTN1	NM_001424013.1		c.105+18C>T		intron	N/A	NP_001410942.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTN1	ENST00000394419.9	TSL:1 MANE Select	c.105+18C>T		intron	N/A	ENSP00000377941.4	P12814-3
	ACTN1	ENST00000538545.6	TSL:1	c.105+18C>T		intron	N/A	ENSP00000439828.2	P12814-4
	ACTN1	ENST00000193403.11	TSL:1	c.105+18C>T		intron	N/A	ENSP00000193403.6	P12814-1

Frequencies

GnomAD3 genomes AF: 0.0203 AC: 3094 AN: 152080 Hom.: 111 Cov.: 33

Gnomad AFR AF: 0.0711

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00608

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0139

GnomAD2 exomes AF: 0.00463 AC: 992 AN: 214268 AF XY: 0.00332

Gnomad AFR exome AF: 0.0709

Gnomad AMR exome AF: 0.00260

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000634

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000236

Gnomad OTH exome AF: 0.00158

GnomAD4 exome AF: 0.00207 AC: 2885 AN: 1394536 Hom.: 111 Cov.: 27 AF XY: 0.00175 AC XY: 1219 AN XY: 695608

African (AFR) AF: 0.0762 AC: 2360 AN: 30970

American (AMR) AF: 0.00309 AC: 129 AN: 41756

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25140

East Asian (EAS) AF: 0.00 AC: 0 AN: 37400

South Asian (SAS) AF: 0.000134 AC: 11 AN: 81836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48436

Middle Eastern (MID) AF: 0.00199 AC: 8 AN: 4016

European-Non Finnish (NFE) AF: 0.000103 AC: 110 AN: 1067222

Other (OTH) AF: 0.00462 AC: 267 AN: 57760

GnomAD4 genome AF: 0.0203 AC: 3096 AN: 152186 Hom.: 111 Cov.: 33 AF XY: 0.0190 AC XY: 1416 AN XY: 74388

African (AFR) AF: 0.0709 AC: 2947 AN: 41540

American (AMR) AF: 0.00608 AC: 93 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 67980

Other (OTH) AF: 0.0137 AC: 29 AN: 2110

Alfa AF: 0.0120 Hom.: 10

Bravo AF: 0.0237

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.5
DANN	Benign	0.92
PhyloP100		1.8
PromoterAI		0.022	Neutral
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: rs185589644; hg19: chr14-69445651;