19-32618998-T-C

Variant names:

• chr19-32618998-T-C
• rs438268
• NM_032139.3:c.2007+262A>G

Variant summary

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

The NM_032139.3(ANKRD27):​c.2007+262A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 152,240 control chromosomes in the GnomAD database, including 47,954 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 0.79 (47954 hom., cov: 34)
• Consequence: ANKRD27 NM_032139.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD27	NM_032139.3	c.2007+262A>G		intron_variant	Intron 20 of 28	ENST00000306065.9	NP_115515.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD27	ENST00000306065.9	c.2007+262A>G		intron_variant	Intron 20 of 28	1	NM_032139.3	ENSP00000304292.3

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119414 AN: 152122 Hom.: 47901 Cov.: 34

Gnomad AFR AF: 0.951

Gnomad AMI AF: 0.829

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.798

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.772

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

GnomAD4 genome AF: 0.785 AC: 119515 AN: 152240 Hom.: 47954 Cov.: 34 AF XY: 0.777 AC XY: 57807 AN XY: 74410

African (AFR) AF: 0.951 AC: 39553 AN: 41576

American (AMR) AF: 0.616 AC: 9424 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.798 AC: 2771 AN: 3472

East Asian (EAS) AF: 0.691 AC: 3574 AN: 5172

South Asian (SAS) AF: 0.717 AC: 3459 AN: 4824

European-Finnish (FIN) AF: 0.685 AC: 7248 AN: 10578

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.748 AC: 50896 AN: 68010

Other (OTH) AF: 0.763 AC: 1610 AN: 2110

Alfa AF: 0.761 Hom.: 79159

Bravo AF: 0.786

Asia WGS AF: 0.650 AC: 2264 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	0.84
DANN	Benign	0.78
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs438268; hg19: chr19-33109904;