7-5527623-C-A

Position:

• chr7-5527623-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001101.5(ACTB):​c.*125G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.053 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000018 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACTB NM_001101.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.13

Genes affected

ACTB (HGNC:132): (actin beta) This gene encodes one of six different actin proteins. Actins are highly conserved proteins that are involved in cell motility, structure, integrity, and intercellular signaling. The encoded protein is a major constituent of the contractile apparatus and one of the two nonmuscle cytoskeletal actins that are ubiquitously expressed. Mutations in this gene cause Baraitser-Winter syndrome 1, which is characterized by intellectual disability with a distinctive facial appearance in human patients. Numerous pseudogenes of this gene have been identified throughout the human genome. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 7-5527623-C-A is Benign according to our data. Variant chr7-5527623-C-A is described in ClinVar as [Benign]. Clinvar id is 1249295.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACTB	NM_001101.5	c.*125G>T		3_prime_UTR_variant	6/6	ENST00000646664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTB	ENST00000646664.1	c.*125G>T		3_prime_UTR_variant	6/6		NM_001101.5	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2953 AN: 55896 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0587

Gnomad AMI AF: 0.0970

Gnomad AMR AF: 0.0521

Gnomad ASJ AF: 0.0377

Gnomad EAS AF: 0.0548

Gnomad SAS AF: 0.0578

Gnomad FIN AF: 0.0491

Gnomad MID AF: 0.0217

Gnomad NFE AF: 0.0500

Gnomad OTH AF: 0.0625

GnomAD4 exome AF: 0.0000178 AC: 20 AN: 1123996 Hom.: 0 Cov.: 18 AF XY: 0.0000159 AC XY: 9 AN XY: 564428

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000223

Gnomad4 NFE exome AF: 0.0000106

Gnomad4 OTH exome AF: 0.0000418

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0529 AC: 2958 AN: 55924 Hom.: 0 Cov.: 0 AF XY: 0.0523 AC XY: 1406 AN XY: 26900

Gnomad4 AFR AF: 0.0589

Gnomad4 AMR AF: 0.0524

Gnomad4 ASJ AF: 0.0377

Gnomad4 EAS AF: 0.0540

Gnomad4 SAS AF: 0.0579

Gnomad4 FIN AF: 0.0491

Gnomad4 NFE AF: 0.0500

Gnomad4 OTH AF: 0.0630

Alfa AF: 0.121 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 17, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.87

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: rs1421339928; hg19: chr7-5567254;