rs7092248

chr10-102502585-A-G

Variant summary

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

The NM_005736.4(ACTR1A):c.48+15T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0076 in 1,614,128 control chromosomes in the GnomAD database, including 786 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 0.040 (399 hom., cov: 33)
  • Exomes 𝑓: 0.0042 (387 hom.)
• Consequence: ACTR1A NM_005736.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.732

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=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACTR1A	NM_005736.4	c.48+15T>C		intron_variant		ENST00000369905.9
ACTR1A	XM_047424427.1	c.-29+15T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTR1A	ENST00000369905.9	c.48+15T>C		intron_variant		1	NM_005736.4	P1
ACTR1A	ENST00000487599.1	c.48+15T>C		intron_variant		5
ACTR1A	ENST00000636707.1	c.48+15T>C		intron_variant, NMD_transcript_variant		5
ACTR1A	ENST00000481044.6	n.55+15T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0404 AC: 6153 AN: 152228 Hom.: 399 Cov.: 33

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0129

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000411

Gnomad OTH AF: 0.0258

GnomAD3 exomes AF: 0.0106 AC: 2665 AN: 251440 Hom.: 166 AF XY: 0.00753 AC XY: 1023 AN XY: 135894

Gnomad AFR exome AF: 0.145

Gnomad AMR exome AF: 0.00653

Gnomad ASJ exome AF: 0.000496

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000392

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000317

Gnomad OTH exome AF: 0.00554

GnomAD4 exome AF: 0.00418 AC: 6109 AN: 1461782 Hom.: 387 Cov.: 30 AF XY: 0.00350 AC XY: 2544 AN XY: 727210

Gnomad4 AFR exome AF: 0.148

Gnomad4 AMR exome AF: 0.00767

Gnomad4 ASJ exome AF: 0.000344

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000161

Gnomad4 OTH exome AF: 0.00907

GnomAD4 genome AF: 0.0405 AC: 6165 AN: 152346 Hom.: 399 Cov.: 33 AF XY: 0.0389 AC XY: 2896 AN XY: 74504

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.0129

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0255

Alfa AF: 0.0287 Hom.: 61

Bravo AF: 0.0458

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	13
Dann	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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: rs7092248; hg19: chr10-104262342;