Genetic Variant ANKRD27:c.526-98T>C (chr19-32643729-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032139.3(ANKRD27):c.526-98T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 1,191,804 control chromosomes in the GnomAD database, including 331,730 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 0.77 ( 46086 hom., cov: 30)

Exomes 𝑓: 0.74 ( 285644 hom. )

Consequence

ANKRD27
NM_032139.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.784

Variant links:

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]

ANKRD27 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD27	NM_032139.3 link	c.526-98T>C		intron_variant	Intron 5 of 28	ENST00000306065.9	NP_115515.2	Q96NW4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD27	ENST00000306065.9 link	c.526-98T>C		intron_variant	Intron 5 of 28	1	NM_032139.3	ENSP00000304292.3		Q96NW4

Frequencies

GnomAD3 genomes

AF:

0.774

AC:

117441

AN:

151754

Hom.:

46045

Cov.:

show subpopulations

Gnomad AFR

AF:

0.902

Gnomad AMI

AF:

0.818

Gnomad AMR

AF:

0.673

Gnomad ASJ

AF:

0.782

Gnomad EAS

AF:

0.680

Gnomad SAS

AF:

0.707

Gnomad FIN

AF:

0.675

Gnomad MID

AF:

0.734

Gnomad NFE

AF:

0.745

Gnomad OTH

AF:

0.775

GnomAD4 exome

AF:

0.738

AC:

767726

AN:

1039932

Hom.:

285644

Cov.:

AF XY:

0.738

AC XY:

392181

AN XY:

531396

show subpopulations

Gnomad4 AFR exome

AF:

0.908

Gnomad4 AMR exome

AF:

0.591

Gnomad4 ASJ exome

AF:

0.782

Gnomad4 EAS exome

AF:

0.711

Gnomad4 SAS exome

AF:

0.713

Gnomad4 FIN exome

AF:

0.698

Gnomad4 NFE exome

AF:

0.745

Gnomad4 OTH exome

AF:

0.749

GnomAD4 genome

AF:

0.774

AC:

117533

AN:

151872

Hom.:

46086

Cov.:

AF XY:

0.766

AC XY:

56812

AN XY:

74172

show subpopulations

Gnomad4 AFR

AF:

0.902

Gnomad4 AMR

AF:

0.672

Gnomad4 ASJ

AF:

0.782

Gnomad4 EAS

AF:

0.681

Gnomad4 SAS

AF:

0.708

Gnomad4 FIN

AF:

0.675

Gnomad4 NFE

AF:

0.745

Gnomad4 OTH

AF:

0.767

Alfa

AF:

0.741

Hom.:

6822

Bravo

AF:

0.779

Asia WGS

AF:

0.643

AC:

2239

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.1

DANN

Benign

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over