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

Variant summary

Our verdict is Benign. The variant received -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

Publications

10 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032139.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD27	NM_032139.3	MANE Select	c.526-98T>C		intron	N/A	NP_115515.2	Q96NW4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANKRD27	ENST00000306065.9	TSL:1 MANE Select	c.526-98T>C	intron	N/A	ENSP00000304292.3	Q96NW4
ANKRD27	ENST00000587352.5	TSL:1	c.526-98T>C	intron	N/A	ENSP00000466138.1	K7ELM1
ANKRD27	ENST00000879691.1		c.526-98T>C	intron	N/A	ENSP00000549750.1

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

African (AFR)

AF:

0.908

AC:

22685

AN:

24976

American (AMR)

AF:

0.591

AC:

24808

AN:

41972

Ashkenazi Jewish (ASJ)

AF:

0.782

AC:

17908

AN:

22906

East Asian (EAS)

AF:

0.711

AC:

26626

AN:

37474

South Asian (SAS)

AF:

0.713

AC:

54325

AN:

76182

European-Finnish (FIN)

AF:

0.698

AC:

33803

AN:

48410

Middle Eastern (MID)

AF:

0.747

AC:

2680

AN:

3590

European-Non Finnish (NFE)

AF:

0.745

AC:

550232

AN:

738148

Other (OTH)

AF:

0.749

AC:

34659

AN:

46274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

10475

20949

31424

41898

52373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11216

22432

33648

44864

56080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.774

AC:

117533

AN:

151872

Hom.:

46086

Cov.:

AF XY:

0.766

AC XY:

56812

AN XY:

74172

show subpopulations

African (AFR)

AF:

0.902

AC:

37363

AN:

41436

American (AMR)

AF:

0.672

AC:

10255

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.782

AC:

2715

AN:

3470

East Asian (EAS)

AF:

0.681

AC:

3492

AN:

5128

South Asian (SAS)

AF:

0.708

AC:

3395

AN:

4798

European-Finnish (FIN)

AF:

0.675

AC:

7092

AN:

10512

Middle Eastern (MID)

AF:

0.752

AC:

221

AN:

294

European-Non Finnish (NFE)

AF:

0.745

AC:

50640

AN:

67958

Other (OTH)

AF:

0.767

AC:

1616

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1275

2550

3826

5101

6376

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

856

1712

2568

3424

4280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.746

Hom.:

7132

Bravo

AF:

0.779

Asia WGS

AF:

0.643

AC:

2239

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.1

(source)

DANN

Benign

0.20

PhyloP100

-0.78

PromoterAI

0.038

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over