rs370106412

Variant names:

• chr7-5527623-CAAAAA-C
• rs370106412
• NM_001101.5:c.*120_*124delTTTTT

Your query was ambiguous. Multiple possible variants found:

• chr7-5527623-CAAAAA-C
• chr7-5527623-CAAAAA-CA
• chr7-5527623-CAAAAA-CAA
• chr7-5527623-CAAAAA-CAAA
• chr7-5527623-CAAAAA-CAAAA
• chr7-5527623-CAAAAA-CAAAAAA
• chr7-5527623-CAAAAA-CAAAAAAA
• chr7-5527623-CAAAAA-CAAAAAAAA
• chr7-5527623-CAAAAA-CAAAAAAAAA
• chr7-5527623-CAAAAA-CAAAAAAAAAA

Variant summary

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

The NM_001101.5(ACTB):​c.*120_*124delTTTTT variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0000089 in 1,123,966 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 0.0 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000089 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACTB NM_001101.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.48
• Publications: 0 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.*120_*124delTTTTT		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.*120_*124delTTTTT		3_prime_UTR	Exon 6 of 6	ENSP00000494750.1	P60709
	ACTB	ENST00000425660.5	TSL:1	n.*911_*915delTTTTT		non_coding_transcript_exon	Exon 7 of 7	ENSP00000409264.1	G5E9R0
	ACTB	ENST00000425660.5	TSL:1	n.*911_*915delTTTTT		3_prime_UTR	Exon 7 of 7	ENSP00000409264.1	G5E9R0

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 59886 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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000890 AC: 10 AN: 1123966 Hom.: 0 AF XY: 0.0000106 AC XY: 6 AN XY: 564410

⚠️ 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: 25164

American (AMR) AF: 0.00 AC: 0 AN: 30472

Ashkenazi Jewish (ASJ) AF: 0.0000966 AC: 2 AN: 20714

East Asian (EAS) AF: 0.00 AC: 0 AN: 35810

South Asian (SAS) AF: 0.00 AC: 0 AN: 68994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3210

European-Non Finnish (NFE) AF: 0.00000940 AC: 8 AN: 851428

Other (OTH) AF: 0.00 AC: 0 AN: 47860

⚠️ 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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 59886 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 28596

African (AFR) AF: 0.00 AC: 0 AN: 15008

American (AMR) AF: 0.00 AC: 0 AN: 5638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1492

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: 0.00 AC: 0 AN: 29704

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.5

Splicing

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

Other links and lift over

dbSNP: rs370106412; hg19: chr7-5567254;