19-15401920-A-G

Position:

• chr19-15401920-A-G

Variant summary

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

The ENST00000397410.10(AKAP8L):​c.363-317T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 152,014 control chromosomes in the GnomAD database, including 50,553 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 0.81 (50553 hom., cov: 32)
• Consequence: AKAP8L ENST00000397410.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.701

Genes affected

AKAP8L (HGNC:29857): (A-kinase anchoring protein 8 like) Enables histone deacetylase binding activity and lamin binding activity. Involved in several processes, including mitotic chromosome condensation; regulation of histone modification; and regulation of mRNA export from nucleus. Located in chromatin; cytoplasm; and nuclear lumen. Part of ribonucleoprotein 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKAP8L	NM_014371.4	c.363-317T>C		intron_variant		ENST00000397410.10	NP_055186.3
AKAP8L	NM_001291478.2	c.180-317T>C		intron_variant			NP_001278407.1
AKAP8L	NR_111971.2	n.326-317T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKAP8L	ENST00000397410.10	c.363-317T>C		intron_variant		1	NM_014371.4	ENSP00000380557	P2

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123324 AN: 151896 Hom.: 50499 Cov.: 32

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.722

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.760

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.788

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

GnomAD4 genome AF: 0.812 AC: 123440 AN: 152014 Hom.: 50553 Cov.: 32 AF XY: 0.812 AC XY: 60337 AN XY: 74274

Gnomad4 AFR AF: 0.900

Gnomad4 AMR AF: 0.823

Gnomad4 ASJ AF: 0.722

Gnomad4 EAS AF: 0.992

Gnomad4 SAS AF: 0.758

Gnomad4 FIN AF: 0.791

Gnomad4 NFE AF: 0.756

Gnomad4 OTH AF: 0.791

Alfa AF: 0.754 Hom.: 38991

Bravo AF: 0.821

Asia WGS AF: 0.878 AC: 3053 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.48

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: rs10775618; hg19: chr19-15512731;