22-37845425-A-G

Variant names:

• chr22-37845425-A-G
• rs6000905
• NM_001349853.2:c.133+2804T>C

Variant summary

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

The NM_001349853.2(ANKRD54):​c.133+2804T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 152,000 control chromosomes in the GnomAD database, including 25,902 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 0.58 (25902 hom., cov: 32)
• Consequence: ANKRD54 NM_001349853.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330
• Publications: 10 publications found

Genes affected

ANKRD54 (HGNC:25185): (ankyrin repeat domain 54) Predicted to enable protein kinase regulator activity. Predicted to be involved in positive regulation of erythrocyte differentiation; regulation of intracellular signal transduction; and regulation of protein kinase activity. Predicted to act upstream of or within nucleocytoplasmic transport. Predicted to be located in midbody. Predicted to be active in cytoplasm and nucleus. [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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349853.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD54	NM_001349853.2		c.133+2804T>C		intron	N/A	NP_001336782.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD54	ENST00000609454.5	TSL:3	c.-28+3512T>C		intron	N/A	ENSP00000477088.1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88037 AN: 151882 Hom.: 25893 Cov.: 32

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.861

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.580 AC: 88084 AN: 152000 Hom.: 25902 Cov.: 32 AF XY: 0.580 AC XY: 43069 AN XY: 74288

African (AFR) AF: 0.518 AC: 21459 AN: 41426

American (AMR) AF: 0.588 AC: 8978 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1958 AN: 3466

East Asian (EAS) AF: 0.860 AC: 4461 AN: 5186

South Asian (SAS) AF: 0.653 AC: 3147 AN: 4820

European-Finnish (FIN) AF: 0.575 AC: 6070 AN: 10564

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.591 AC: 40133 AN: 67952

Other (OTH) AF: 0.582 AC: 1226 AN: 2106

Alfa AF: 0.591 Hom.: 15675

Bravo AF: 0.578

Asia WGS AF: 0.708 AC: 2465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.3
DANN	Benign	0.76
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6000905; hg19: chr22-38241432;