rs1578215

Variant names:

• chr1-17793106-G-A
• rs1578215
• NM_030812.3:c.-24-29879G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030812.3(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 NM_030812.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ACTL8	NM_030812.3	c.-24-29879G>A		intron_variant	Intron 1 of 2	ENST00000375406.2	NP_110439.2
ACTL8	XM_011542212.3	c.-24-29879G>A		intron_variant	Intron 1 of 2		XP_011540514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTL8	ENST00000375406.2	c.-24-29879G>A		intron_variant	Intron 1 of 2	1	NM_030812.3	ENSP00000364555.1

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

African (AFR) AF: 0.130 AC: 5389 AN: 41544

American (AMR) AF: 0.160 AC: 2452 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0592 AC: 205 AN: 3464

East Asian (EAS) AF: 0.113 AC: 587 AN: 5178

South Asian (SAS) AF: 0.0353 AC: 170 AN: 4822

European-Finnish (FIN) AF: 0.123 AC: 1300 AN: 10602

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0997 AC: 6778 AN: 68010

Other (OTH) AF: 0.0946 AC: 200 AN: 2114

Alfa AF: 0.100 Hom.: 1750

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
PhyloP100		1.4
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: rs1578215; hg19: chr1-18119601; COSMIC: COSV64860598;