chr7-100643148-A-G

Variant names:

• chr7-100643148-A-G
• rs1052897
• NM_016188.5:c.*98T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016188.5(ACTL6B):​c.*98T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACTL6B NM_016188.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180
• Publications: 14 publications found

Genes affected

ACTL6B (HGNC:160): (actin like 6B) The protein encoded by this gene is a member of a family of actin-related proteins (ARPs) which share significant amino acid sequence identity to conventional actins. Both actins and ARPs have an actin fold, which is an ATP-binding cleft, as a common feature. The ARPs are involved in diverse cellular processes, including vesicular transport, spindle orientation, nuclear migration and chromatin remodeling. This gene encodes a subunit of the BAF (BRG1/brm-associated factor) complex in mammals, which is functionally related to SWI/SNF complex in S. cerevisiae and Drosophila; the latter is thought to facilitate transcriptional activation of specific genes by antagonizing chromatin-mediated transcriptional repression. This subunit may be involved in the regulation of genes by structural modulation of their chromatin, specifically in the brain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACTL6B Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 76

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• intellectual developmental disorder with severe speech and ambulation defects

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016188.5. 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
	ACTL6B	NM_016188.5	MANE Select	c.*98T>C		3_prime_UTR	Exon 14 of 14	NP_057272.1	O94805
	ACTL6B	NR_134539.2		n.1490T>C		non_coding_transcript_exon	Exon 14 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTL6B	ENST00000160382.10	TSL:1 MANE Select	c.*98T>C		3_prime_UTR	Exon 14 of 14	ENSP00000160382.5	O94805
	ACTL6B	ENST00000970942.1		c.*98T>C		3_prime_UTR	Exon 15 of 15	ENSP00000641001.1
	ACTL6B	ENST00000970941.1		c.*98T>C		3_prime_UTR	Exon 13 of 13	ENSP00000641000.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1089554 Hom.: 0 Cov.: 14 AF XY: 0.00 AC XY: 0 AN XY: 550822

African (AFR) AF: 0.00 AC: 0 AN: 25574

American (AMR) AF: 0.00 AC: 0 AN: 37242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21736

East Asian (EAS) AF: 0.00 AC: 0 AN: 37194

South Asian (SAS) AF: 0.00 AC: 0 AN: 74832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49246

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4882

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 791382

Other (OTH) AF: 0.00 AC: 0 AN: 47466

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.9
DANN	Benign	0.77
PhyloP100		0.018
PromoterAI		-0.0042	Neutral

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: rs1052897; hg19: chr7-100240771;