10-88935012-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NR_125373.1(ACTA2-AS1):n.637C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00484 in 569,254 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (34 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (8 hom.)
• Consequence: ACTA2-AS1 NR_125373.1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.91

Genes affected

ACTA2-AS1 (HGNC:45169): (ACTA2 antisense RNA 1)

STAMBPL1 (HGNC:24105): (STAM binding protein like 1) Predicted to enable Lys63-specific deubiquitinase activity and thiol-dependent deubiquitinase. Predicted to be involved in protein K63-linked deubiquitination. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-88935012-C-T is Benign according to our data. Variant chr10-88935012-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1198277.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0137 (2081/152054) while in subpopulation AFR AF= 0.0474 (1967/41464). AF 95% confidence interval is 0.0457. There are 34 homozygotes in gnomad4. There are 983 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 34 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACTA2-AS1	NR_125373.1	n.637C>T		non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTA2-AS1	ENST00000437930.4	n.678C>T		non_coding_transcript_exon_variant	3/5	2
STAMBPL1	ENST00000371927.7	c.1254+12576C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0137 AC: 2076 AN: 151940 Hom.: 34 Cov.: 32

Gnomad AFR AF: 0.0474

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0100

GnomAD4 exome AF: 0.00162 AC: 675 AN: 417200 Hom.: 8 Cov.: 6 AF XY: 0.00135 AC XY: 298 AN XY: 220130

Gnomad4 AFR exome AF: 0.0474

Gnomad4 AMR exome AF: 0.00246

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000646

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000802

Gnomad4 OTH exome AF: 0.00318

GnomAD4 genome AF: 0.0137 AC: 2081 AN: 152054 Hom.: 34 Cov.: 32 AF XY: 0.0132 AC XY: 983 AN XY: 74328

Gnomad4 AFR AF: 0.0474

Gnomad4 AMR AF: 0.00504

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00993

Alfa AF: 0.00908 Hom.: 0

Bravo AF: 0.0149

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 08, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.097
Dann	Benign	0.60

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs77086884; hg19: chr10-90694769;