rs259228

Variant names:

• chr19-32643729-A-C
• rs259228
• NM_032139.3:c.526-98T>G

Your query was ambiguous. Multiple possible variants found:

• chr19-32643729-A-C
• chr19-32643729-A-G
• chr19-32643729-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032139.3(ANKRD27):​c.526-98T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKRD27 NM_032139.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.784
• Publications: 10 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD27	ENST00000306065.9	TSL:1 MANE Select	c.526-98T>G		intron	N/A	ENSP00000304292.3
	ANKRD27	ENST00000587352.5	TSL:1	c.526-98T>G		intron	N/A	ENSP00000466138.1
	ANKRD27	ENST00000593232.5	TSL:2	n.57T>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1041592 Hom.: 0 Cov.: 14 AF XY: 0.00 AC XY: 0 AN XY: 532194

African (AFR) AF: 0.00 AC: 0 AN: 24994

American (AMR) AF: 0.00 AC: 0 AN: 42032

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22936

East Asian (EAS) AF: 0.00 AC: 0 AN: 37484

South Asian (SAS) AF: 0.00 AC: 0 AN: 76232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48452

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3598

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 739548

Other (OTH) AF: 0.00 AC: 0 AN: 46316

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 7132

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.94
DANN	Benign	0.33
PhyloP100		-0.78
PromoterAI		-0.017	Neutral

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: rs259228; hg19: chr19-33134635;