7-5527651-CAAAAA-CAAAAAAA

Variant names:

• chr7-5527651-C-CAA
• rs372205322
• NM_001101.5:c.*95_*96dupTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001101.5(ACTB):​c.*95_*96dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000528 in 1,326,666 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: ACTB NM_001101.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270

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.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000165 (24/145470) while in subpopulation AFR AF= 0.000431 (17/39472). AF 95% confidence interval is 0.000274. There are 0 homozygotes in gnomad4. There are 10 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTB	NM_001101.5	c.*95_*96dupTT		3_prime_UTR_variant	Exon 6 of 6	ENST00000646664.1	NP_001092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTB	ENST00000646664	c.*95_*96dupTT		3_prime_UTR_variant	Exon 6 of 6		NM_001101.5	ENSP00000494750.1

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 23 AN: 145404 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000406

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000273

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: 0.0000455

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000389 AC: 46 AN: 1181196 Hom.: 0 Cov.: 30 AF XY: 0.0000356 AC XY: 21 AN XY: 589760

Gnomad4 AFR exome AF: 0.000420

Gnomad4 AMR exome AF: 0.0000627

Gnomad4 ASJ exome AF: 0.0000933

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000311

Gnomad4 OTH exome AF: 0.0000603

GnomAD4 genome AF: 0.000165 AC: 24 AN: 145470 Hom.: 0 Cov.: 31 AF XY: 0.000141 AC XY: 10 AN XY: 70672

Gnomad4 AFR AF: 0.000431

Gnomad4 AMR AF: 0.000273

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000455

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs372205322; hg19: chr7-5567282;