rs1578215

Positions:

• chr1-17793106-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000375406.2(ACTL8):​c.-24-29879G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,236 control chromosomes in the GnomAD database, including 1,059 homozygotes. 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: 𝑓 0.11 (1059 hom., cov: 33)
• Consequence: ACTL8 ENST00000375406.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39

Genes affected

ACTL8 (HGNC:24018): (actin like 8) Involved in epithelial cell differentiation. Predicted to be located in cytoplasm. Predicted to be part of dynactin complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTL8	NM_030812.3	c.-24-29879G>A		intron_variant		ENST00000375406.2	NP_110439.2
ACTL8	XM_011542212.3	c.-24-29879G>A		intron_variant			XP_011540514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTL8	ENST00000375406.2	c.-24-29879G>A		intron_variant		1	NM_030812.3	ENSP00000364555	P1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17130 AN: 152118 Hom.: 1056 Cov.: 33

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.0592

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0354

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0997

Gnomad OTH AF: 0.0951

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.113 AC: 17161 AN: 152236 Hom.: 1059 Cov.: 33 AF XY: 0.113 AC XY: 8408 AN XY: 74424

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.0592

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.0353

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.0997

Gnomad4 OTH AF: 0.0946

Alfa AF: 0.0959 Hom.: 1083

Bravo AF: 0.118

Asia WGS AF: 0.0740 AC: 260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs1578215; hg19: chr1-18119601; COSMIC: COSV64860598;