NM_001101.5:c.*121_*124delTTTT

Variant names:

• chr7-5527623-CAAAA-C
• rs370106412
• NM_001101.5:c.*121_*124delTTTT

Variant summary

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

The NM_001101.5(ACTB):​c.*121_*124delTTTT variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0000524 in 1,183,224 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000033 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000053 (0 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.*121_*124delTTTT		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.*121_*124delTTTT		3_prime_UTR	Exon 6 of 6	ENSP00000494750.1	P60709
	ACTB	ENST00000425660.5	TSL:1	n.*912_*915delTTTT		non_coding_transcript_exon	Exon 7 of 7	ENSP00000409264.1	G5E9R0
	ACTB	ENST00000425660.5	TSL:1	n.*912_*915delTTTT		3_prime_UTR	Exon 7 of 7	ENSP00000409264.1	G5E9R0

Frequencies

GnomAD3 genomes AF: 0.0000334 AC: 2 AN: 59888 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000670

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000539

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000534 AC: 60 AN: 1123304 Hom.: 0 AF XY: 0.0000532 AC XY: 30 AN XY: 564076

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

African (AFR) AF: 0.00 AC: 0 AN: 25148

American (AMR) AF: 0.000131 AC: 4 AN: 30460

Ashkenazi Jewish (ASJ) AF: 0.000145 AC: 3 AN: 20704

East Asian (EAS) AF: 0.00 AC: 0 AN: 35796

South Asian (SAS) AF: 0.000116 AC: 8 AN: 68974

European-Finnish (FIN) AF: 0.0000248 AC: 1 AN: 40270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3206

European-Non Finnish (NFE) AF: 0.0000494 AC: 42 AN: 850910

Other (OTH) AF: 0.0000418 AC: 2 AN: 47836

⚠️ 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: 0.0000334 AC: 2 AN: 59920 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 28626

African (AFR) AF: 0.00 AC: 0 AN: 15048

American (AMR) AF: 0.00 AC: 0 AN: 5644

Ashkenazi Jewish (ASJ) AF: 0.000670 AC: 1 AN: 1492

East Asian (EAS) AF: 0.00 AC: 0 AN: 1780

South Asian (SAS) AF: 0.000539 AC: 1 AN: 1854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3120

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 98

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 29702

Other (OTH) AF: 0.00 AC: 0 AN: 828

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.5

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;