2-240525498-A-C

Variant names:

• chr2-240525498-A-C
• rs4398270
• NM_001282771.3:c.1335+187T>G

Variant summary

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

The NM_001282771.3(ANKMY1):​c.1335+187T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 152,106 control chromosomes in the GnomAD database, including 41,477 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 0.73 (41477 hom., cov: 32)
• Consequence: ANKMY1 NM_001282771.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.400
• Publications: 4 publications found

Genes affected

ANKMY1 (HGNC:20987): (ankyrin repeat and MYND domain containing 1) Predicted to enable metal ion binding activity. [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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282771.3. 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
	ANKMY1	NM_001282771.3	MANE Select	c.1335+187T>G		intron	N/A	NP_001269700.1
	ANKMY1	NM_001354023.3		c.1335+187T>G		intron	N/A	NP_001340952.1
	ANKMY1	NM_001393462.1		c.1251+187T>G		intron	N/A	NP_001380391.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKMY1	ENST00000401804.6	TSL:1 MANE Select	c.1335+187T>G		intron	N/A	ENSP00000385887.1
	ANKMY1	ENST00000272972.7	TSL:1	c.1068+187T>G		intron	N/A	ENSP00000272972.3
	ANKMY1	ENST00000403283.6	TSL:1	c.882+187T>G		intron	N/A	ENSP00000383968.1

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111664 AN: 151988 Hom.: 41415 Cov.: 32

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.696

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.835

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.739

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

GnomAD4 genome AF: 0.735 AC: 111784 AN: 152106 Hom.: 41477 Cov.: 32 AF XY: 0.740 AC XY: 54992 AN XY: 74352

African (AFR) AF: 0.825 AC: 34226 AN: 41508

American (AMR) AF: 0.662 AC: 10110 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.696 AC: 2414 AN: 3468

East Asian (EAS) AF: 0.855 AC: 4423 AN: 5172

South Asian (SAS) AF: 0.836 AC: 4028 AN: 4818

European-Finnish (FIN) AF: 0.725 AC: 7677 AN: 10582

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.683 AC: 46454 AN: 67976

Other (OTH) AF: 0.742 AC: 1563 AN: 2106

Alfa AF: 0.717 Hom.: 15532

Bravo AF: 0.734

Asia WGS AF: 0.836 AC: 2911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.0
DANN	Benign	0.47
PhyloP100		-0.40
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: rs4398270; hg19: chr2-241464915;