rs7092248

Variant names:

• chr10-102502585-A-G
• rs7092248
• NM_005736.4:c.48+15T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

SUFU (HGNC:16466): (SUFU negative regulator of hedgehog signaling) The Hedgehog signaling pathway plays an important role in early human development. The pathway is a signaling cascade that plays a role in pattern formation and cellular proliferation during development. This gene encodes a negative regulator of the hedgehog signaling pathway. Defects in this gene are a cause of medulloblastoma. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

SUFU Gene-Disease associations (from GenCC):

• medulloblastoma

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• nevoid basal cell carcinoma syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Illumina, Genomics England PanelApp
• basal cell nevus syndrome 2

  Inheritance: AD Classification: STRONG Submitted by: G2P
• ocular motor apraxia, Cogan type

  Inheritance: AD Classification: STRONG Submitted by: Franklin by Genoox
• Joubert syndrome 32

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• Joubert syndrome

  Inheritance: AR, AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
• apraxia

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• ciliopathy

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005736.4. 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
	ACTR1A	NM_005736.4	MANE Select	c.48+15T>C		intron	N/A	NP_005727.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTR1A	ENST00000369905.9	TSL:1 MANE Select	c.48+15T>C		intron	N/A	ENSP00000358921.4
	ACTR1A	ENST00000972053.1		c.48+15T>C		intron	N/A	ENSP00000642112.1
	ACTR1A	ENST00000900302.1		c.48+15T>C		intron	N/A	ENSP00000570361.1

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

GnomAD2 exomes AF: 0.0106 AC: 2665 AN: 251440 AF XY: 0.00753

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 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

African (AFR) AF: 0.148 AC: 4951 AN: 33462

American (AMR) AF: 0.00767 AC: 343 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000344 AC: 9 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000464 AC: 40 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00676 AC: 39 AN: 5768

European-Non Finnish (NFE) AF: 0.000161 AC: 179 AN: 1111932

Other (OTH) AF: 0.00907 AC: 548 AN: 60394

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

African (AFR) AF: 0.141 AC: 5873 AN: 41562

American (AMR) AF: 0.0129 AC: 197 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68038

Other (OTH) AF: 0.0255 AC: 54 AN: 2116

Alfa AF: 0.0312 Hom.: 72

Bravo AF: 0.0458

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Benign	0.56
PhyloP100		0.73
PromoterAI		-0.0034	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
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: rs7092248; hg19: chr10-104262342;