rs4805784

Positions:

• chr19-32627860-C-A
• chr19-32627860-C-G
• chr19-32627860-C-T

Variant summary

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

The NM_032139.3(ANKRD27):​c.1420+223G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 152,182 control chromosomes in the GnomAD database, including 34,167 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 0.67 (34167 hom., cov: 35)
• Consequence: ANKRD27 NM_032139.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.21

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD27	NM_032139.3	c.1420+223G>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.1420+223G>T		intron_variant		1	NM_032139.3	ENSP00000304292	P1
ANKRD27	ENST00000591100.6	c.502+223G>T		intron_variant		5		ENSP00000464751

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101624 AN: 152064 Hom.: 34137 Cov.: 35

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.666

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

GnomAD4 genome AF: 0.668 AC: 101696 AN: 152182 Hom.: 34167 Cov.: 35 AF XY: 0.663 AC XY: 49357 AN XY: 74392

Gnomad4 AFR AF: 0.713

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.664

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.671

Gnomad4 OTH AF: 0.660

Alfa AF: 0.665 Hom.: 47491

Bravo AF: 0.667

Asia WGS AF: 0.594 AC: 2067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.070
DANN	Benign	0.68

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: rs4805784; hg19: chr19-33118766; COSMIC: COSV60130076;