rs17692896

Positions:

• chr19-32598525-G-A

Variant summary

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

The ENST00000306065.9(ANKRD27):​c.2920-147C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0527 in 699,950 control chromosomes in the GnomAD database, including 1,254 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 0.045 (231 hom., cov: 33)
  • Exomes 𝑓: 0.055 (1023 hom.)
• Consequence: ANKRD27 ENST00000306065.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279

Genes affected

ANKRD27 (HGNC:25310): (ankyrin repeat domain 27) Enables guanyl-nucleotide exchange factor activity and small GTPase binding activity. Involved in endocytic recycling and negative regulation of SNARE complex assembly. Acts upstream of or within early endosome to late endosome transport. Located in endosome; lysosome; and plasma membrane. Implicated in eosinophilic esophagitis. [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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD27	NM_032139.3	c.2920-147C>T		intron_variant		ENST00000306065.9	NP_115515.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD27	ENST00000306065.9	c.2920-147C>T		intron_variant		1	NM_032139.3	ENSP00000304292	P1
ANKRD27	ENST00000587667.1	n.389-147C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0451 AC: 6868 AN: 152148 Hom.: 231 Cov.: 33

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0279

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0476

Gnomad FIN AF: 0.0841

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0682

Gnomad OTH AF: 0.0306

GnomAD4 exome AF: 0.0548 AC: 29989 AN: 547684 Hom.: 1023 AF XY: 0.0545 AC XY: 15719 AN XY: 288232

Gnomad4 AFR exome AF: 0.0111

Gnomad4 AMR exome AF: 0.0193

Gnomad4 ASJ exome AF: 0.0327

Gnomad4 EAS exome AF: 0.000125

Gnomad4 SAS exome AF: 0.0465

Gnomad4 FIN exome AF: 0.0808

Gnomad4 NFE exome AF: 0.0652

Gnomad4 OTH exome AF: 0.0526

GnomAD4 genome AF: 0.0451 AC: 6870 AN: 152266 Hom.: 231 Cov.: 33 AF XY: 0.0445 AC XY: 3311 AN XY: 74456

Gnomad4 AFR AF: 0.0110

Gnomad4 AMR AF: 0.0279

Gnomad4 ASJ AF: 0.0334

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0480

Gnomad4 FIN AF: 0.0841

Gnomad4 NFE AF: 0.0682

Gnomad4 OTH AF: 0.0302

Alfa AF: 0.0614 Hom.: 197

Bravo AF: 0.0388

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.7
DANN	Benign	0.50

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: rs17692896; hg19: chr19-33089431;