NM_001101.5:c.*122_*124delTTT

Variant names:

• chr7-5527623-CAAA-C
• rs370106412
• NM_001101.5:c.*122_*124delTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001101.5(ACTB):​c.*122_*124delTTT variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.000591 in 1,179,908 control chromosomes in the GnomAD database, including 1 homozygotes. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000050 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00062 (1 hom.)
• Consequence: ACTB NM_001101.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.48
• Publications: 1 publications found

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]

ACTB Gene-Disease associations (from GenCC):

• Baraitser-Winter cerebrofrontofacial syndrome

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

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

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

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001101.5. 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
	ACTB	NM_001101.5	MANE Select	c.*122_*124delTTT		3_prime_UTR	Exon 6 of 6	NP_001092.1	P60709

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTB	ENST00000646664.1	MANE Select	c.*122_*124delTTT		3_prime_UTR	Exon 6 of 6	ENSP00000494750.1	P60709
	ACTB	ENST00000425660.5	TSL:1	n.*913_*915delTTT		non_coding_transcript_exon	Exon 7 of 7	ENSP00000409264.1	G5E9R0
	ACTB	ENST00000425660.5	TSL:1	n.*913_*915delTTT		3_prime_UTR	Exon 7 of 7	ENSP00000409264.1	G5E9R0

Frequencies

GnomAD3 genomes AF: 0.0000501 AC: 3 AN: 59880 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000101

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000620 AC: 694 AN: 1120028 Hom.: 1 AF XY: 0.000656 AC XY: 369 AN XY: 562444

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000559 AC: 14 AN: 25054

American (AMR) AF: 0.000758 AC: 23 AN: 30356

Ashkenazi Jewish (ASJ) AF: 0.000631 AC: 13 AN: 20598

East Asian (EAS) AF: 0.000281 AC: 10 AN: 35638

South Asian (SAS) AF: 0.000625 AC: 43 AN: 68800

European-Finnish (FIN) AF: 0.000548 AC: 22 AN: 40134

Middle Eastern (MID) AF: 0.000312 AC: 1 AN: 3204

European-Non Finnish (NFE) AF: 0.000640 AC: 543 AN: 848572

Other (OTH) AF: 0.000524 AC: 25 AN: 47672

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000501 AC: 3 AN: 59880 Hom.: 0 Cov.: 30 AF XY: 0.0000350 AC XY: 1 AN XY: 28592

African (AFR) AF: 0.00 AC: 0 AN: 15006

American (AMR) AF: 0.00 AC: 0 AN: 5636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1490

East Asian (EAS) AF: 0.00 AC: 0 AN: 1796

South Asian (SAS) AF: 0.00 AC: 0 AN: 1856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3118

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 100

European-Non Finnish (NFE) AF: 0.000101 AC: 3 AN: 29704

Other (OTH) AF: 0.00 AC: 0 AN: 820

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.5
Mutation Taster		=100/0	polymorphism

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: rs370106412; hg19: chr7-5567254;