rs5870

Positions:

• chr10-102479343-T-C
• chr10-102479343-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005736.4(ACTR1A):​c.*1520A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 378,602 control chromosomes in the GnomAD database, including 50,486 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 0.51 (19808 hom., cov: 33)
  • Exomes 𝑓: 0.51 (30678 hom.)
• Consequence: ACTR1A NM_005736.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.860

Genes affected

ACTR1A (HGNC:167): (actin related protein 1A) This gene encodes a 42.6 kD subunit of dynactin, a macromolecular complex consisting of 10-11 subunits ranging in size from 22 to 150 kD. Dynactin binds to both microtubules and cytoplasmic dynein. It is involved in a diverse array of cellular functions, including ER-to-Golgi transport, the centripetal movement of lysosomes and endosomes, spindle formation, chromosome movement, nuclear positioning, and axonogenesis. This subunit is present in 8-13 copies per dynactin molecule, and is the most abundant molecule in the dynactin complex. It is an actin-related protein, and is approximately 60% identical at the amino acid level to conventional actin. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTR1A	NM_005736.4	c.*1520A>G		3_prime_UTR_variant	11/11	ENST00000369905.9	NP_005727.1
ACTR1A	XM_047424427.1	c.*1520A>G		3_prime_UTR_variant	10/10		XP_047280383.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTR1A	ENST00000369905.9	c.*1520A>G		3_prime_UTR_variant	11/11	1	NM_005736.4	ENSP00000358921	P1
ACTR1A	ENST00000487599.1	c.*1590A>G		3_prime_UTR_variant	10/10	5		ENSP00000473334
ACTR1A	ENST00000470322.5	n.3406A>G		non_coding_transcript_exon_variant	4/4	2
ACTR1A	ENST00000636707.1	c.657+4817A>G		intron_variant, NMD_transcript_variant		5		ENSP00000490634

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76916 AN: 151990 Hom.: 19803 Cov.: 33

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.532

GnomAD4 exome AF: 0.514 AC: 116386 AN: 226494 Hom.: 30678 Cov.: 4 AF XY: 0.513 AC XY: 63246 AN XY: 123224

Gnomad4 AFR exome AF: 0.467

Gnomad4 AMR exome AF: 0.349

Gnomad4 ASJ exome AF: 0.660

Gnomad4 EAS exome AF: 0.324

Gnomad4 SAS exome AF: 0.490

Gnomad4 FIN exome AF: 0.536

Gnomad4 NFE exome AF: 0.545

Gnomad4 OTH exome AF: 0.522

GnomAD4 genome AF: 0.506 AC: 76935 AN: 152108 Hom.: 19808 Cov.: 33 AF XY: 0.501 AC XY: 37241 AN XY: 74334

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.521

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.532

Alfa AF: 0.537 Hom.: 38116

Bravo AF: 0.494

Asia WGS AF: 0.392 AC: 1366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.61

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: rs5870; hg19: chr10-104239100; COSMIC: COSV53267194; COSMIC: COSV53267194;