rs4380978

Positions:

• chr8-144375777-G-C
• chr8-144375777-G-T

Variant summary

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

The NM_174922.5(ADCK5):​c.12+1670G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 592,950 control chromosomes in the GnomAD database, including 56,529 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 0.42 (14189 hom., cov: 33)
  • Exomes 𝑓: 0.43 (42340 hom.)
• Consequence: ADCK5 NM_174922.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

Genes affected

ADCK5 (HGNC:21738): (aarF domain containing kinase 5) Predicted to enable protein serine/threonine kinase activity. Predicted to be involved in protein phosphorylation. Predicted to be integral component of membrane. [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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCK5	NM_174922.5	c.12+1670G>C		intron_variant		ENST00000308860.11	NP_777582.4
ADCK5	XM_011516907.4	c.234+140G>C		intron_variant			XP_011515209.1
ADCK5	XM_017013174.2	c.-190+1885G>C		intron_variant			XP_016868663.1
ADCK5	XM_047421456.1	c.234+140G>C		intron_variant			XP_047277412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCK5	ENST00000308860.11	c.12+1670G>C		intron_variant		1	NM_174922.5	ENSP00000310547	P1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64437 AN: 151990 Hom.: 14177 Cov.: 33

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.411

GnomAD4 exome AF: 0.433 AC: 191006 AN: 440842 Hom.: 42340 AF XY: 0.434 AC XY: 89778 AN XY: 206800

Gnomad4 AFR exome AF: 0.329

Gnomad4 AMR exome AF: 0.520

Gnomad4 ASJ exome AF: 0.342

Gnomad4 EAS exome AF: 0.656

Gnomad4 SAS exome AF: 0.583

Gnomad4 FIN exome AF: 0.467

Gnomad4 NFE exome AF: 0.432

Gnomad4 OTH exome AF: 0.431

GnomAD4 genome AF: 0.424 AC: 64475 AN: 152108 Hom.: 14189 Cov.: 33 AF XY: 0.430 AC XY: 31943 AN XY: 74364

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.641

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.411

Alfa AF: 0.274 Hom.: 674

Bravo AF: 0.422

Asia WGS AF: 0.568 AC: 1974 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.88
DANN	Benign	0.30

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: rs4380978; hg19: chr8-145599466;