ENST00000609813.1:n.488A>G

Variant names:

• chr7-5557218-A-G
• rs1474445
• ENST00000609813.1:n.488A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000609813.1(ENSG00000272719):​n.488A>G 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 0.215 in 152,228 control chromosomes in the GnomAD database, including 3,665 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 0.21 (3665 hom., cov: 32)
  • Exomes 𝑓: 0.27 (0 hom.)
• Consequence: ENSG00000272719 ENST00000609813.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.471
• Publications: 6 publications found

Genes affected

ENSG00000272719 (HGNC:):

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]

ACTB Gene-Disease associations (from GenCC):

• Baraitser-Winter cerebrofrontofacial syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Baraitser-Winter syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, PanelApp Australia, G2P
• developmental malformations-deafness-dystonia syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Illumina
• ACTB-associated syndromic thrombocytopenia

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000609813.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000272719	ENST00000609813.1	TSL:6	n.488A>G		non_coding_transcript_exon	Exon 1 of 1
	ACTB	ENST00000675515.1		c.-7+6496T>C		intron	N/A	ENSP00000501862.1
	ACTB	ENST00000443528.5	TSL:4	c.-7+5356T>C		intron	N/A	ENSP00000393951.1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32670 AN: 152082 Hom.: 3672 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.207

GnomAD4 exome AF: 0.269 AC: 7 AN: 26 Hom.: 0 Cov.: 0 AF XY: 0.200 AC XY: 4 AN XY: 20

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 3 AN: 6

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 2 AN: 8

Other (OTH) AF: 0.333 AC: 2 AN: 6

GnomAD4 genome AF: 0.215 AC: 32685 AN: 152202 Hom.: 3665 Cov.: 32 AF XY: 0.221 AC XY: 16474 AN XY: 74410

African (AFR) AF: 0.225 AC: 9326 AN: 41534

American (AMR) AF: 0.183 AC: 2798 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 820 AN: 3468

East Asian (EAS) AF: 0.171 AC: 886 AN: 5188

South Asian (SAS) AF: 0.281 AC: 1359 AN: 4828

European-Finnish (FIN) AF: 0.318 AC: 3368 AN: 10580

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13475 AN: 68020

Other (OTH) AF: 0.208 AC: 439 AN: 2114

Alfa AF: 0.195 Hom.: 4177

Bravo AF: 0.200

Asia WGS AF: 0.230 AC: 798 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.8
DANN	Benign	0.85
PhyloP100		0.47

Splicing

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

Other links and lift over

dbSNP: rs1474445; hg19: chr7-5596849;