rs1052897

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr7-100643148-A-T
• chr7-100643148-A-C
• chr7-100643148-A-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016188.5(ACTL6B):​c.*98T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 1,240,224 control chromosomes in the GnomAD database, including 447,348 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.88 (59308 hom., cov: 30)
  • Exomes 𝑓: 0.84 (388040 hom.)
• Consequence: ACTL6B NM_016188.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 7-100643148-A-T is Benign according to our data. Variant chr7-100643148-A-T is described in ClinVar as Benign. ClinVar VariationId is 1188858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

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>A		3_prime_UTR	Exon 14 of 14	NP_057272.1	O94805
	ACTL6B	NR_134539.2		n.1490T>A		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>A		3_prime_UTR	Exon 14 of 14	ENSP00000160382.5	O94805
	ACTL6B	ENST00000970942.1		c.*98T>A		3_prime_UTR	Exon 15 of 15	ENSP00000641001.1
	ACTL6B	ENST00000970941.1		c.*98T>A		3_prime_UTR	Exon 13 of 13	ENSP00000641000.1

Frequencies

GnomAD3 genomes AF: 0.881 AC: 133836 AN: 151968 Hom.: 59250 Cov.: 30

Gnomad AFR AF: 0.969

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.882

Gnomad EAS AF: 0.906

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.875

GnomAD4 exome AF: 0.843 AC: 917506 AN: 1088138 Hom.: 388040 Cov.: 14 AF XY: 0.839 AC XY: 461575 AN XY: 550184

African (AFR) AF: 0.975 AC: 24918 AN: 25564

American (AMR) AF: 0.899 AC: 33463 AN: 37216

Ashkenazi Jewish (ASJ) AF: 0.878 AC: 19084 AN: 21724

East Asian (EAS) AF: 0.933 AC: 34665 AN: 37170

South Asian (SAS) AF: 0.760 AC: 56790 AN: 74720

European-Finnish (FIN) AF: 0.830 AC: 40818 AN: 49204

Middle Eastern (MID) AF: 0.849 AC: 4143 AN: 4880

European-Non Finnish (NFE) AF: 0.839 AC: 663015 AN: 790242

Other (OTH) AF: 0.856 AC: 40610 AN: 47418

GnomAD4 genome AF: 0.881 AC: 133953 AN: 152086 Hom.: 59308 Cov.: 30 AF XY: 0.879 AC XY: 65375 AN XY: 74350

African (AFR) AF: 0.969 AC: 40200 AN: 41500

American (AMR) AF: 0.904 AC: 13803 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 3059 AN: 3468

East Asian (EAS) AF: 0.906 AC: 4686 AN: 5172

South Asian (SAS) AF: 0.760 AC: 3659 AN: 4812

European-Finnish (FIN) AF: 0.824 AC: 8706 AN: 10570

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.839 AC: 57049 AN: 67982

Other (OTH) AF: 0.875 AC: 1842 AN: 2106

Alfa AF: 0.812 Hom.: 2874

Bravo AF: 0.893

Asia WGS AF: 0.834 AC: 2903 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Developmental and epileptic encephalopathy, 76 (1)
-	-	1	Intellectual developmental disorder with severe speech and ambulation defects (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.5
DANN	Benign	0.65
PhyloP100		0.018
PromoterAI		-0.00050	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV99355493; COSMIC: COSV99355493;