2-240555596-C-G

Variant names:

• chr2-240555596-C-G
• rs4305276
• NM_001282771.3:c.147-541G>C

Variant summary

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

The NM_001282771.3(ANKMY1):​c.147-541G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 155,640 control chromosomes in the GnomAD database, including 32,719 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 0.64 (31736 hom., cov: 33)
  • Exomes 𝑓: 0.67 (983 hom.)
• Consequence: ANKMY1 NM_001282771.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15
• Publications: 13 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.809 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.147-541G>C		intron	N/A	NP_001269700.1
	ANKMY1	NM_001354023.3		c.147-541G>C		intron	N/A	NP_001340952.1
	ANKMY1	NM_001393462.1		c.63-541G>C		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.147-541G>C		intron	N/A	ENSP00000385887.1
	ANKMY1	ENST00000272972.7	TSL:1	c.-121-541G>C		intron	N/A	ENSP00000272972.3
	ANKMY1	ENST00000403283.6	TSL:1	c.384-541G>C		intron	N/A	ENSP00000383968.1

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97354 AN: 151288 Hom.: 31706 Cov.: 33

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.664

GnomAD4 exome AF: 0.667 AC: 2822 AN: 4234 Hom.: 983 Cov.: 0 AF XY: 0.679 AC XY: 1595 AN XY: 2348

African (AFR) AF: 0.459 AC: 45 AN: 98

American (AMR) AF: 0.592 AC: 565 AN: 954

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 23 AN: 40

East Asian (EAS) AF: 0.833 AC: 120 AN: 144

South Asian (SAS) AF: 0.809 AC: 304 AN: 376

European-Finnish (FIN) AF: 0.820 AC: 41 AN: 50

Middle Eastern (MID) AF: 1.00 AC: 4 AN: 4

European-Non Finnish (NFE) AF: 0.672 AC: 1607 AN: 2392

Other (OTH) AF: 0.642 AC: 113 AN: 176

GnomAD4 genome AF: 0.644 AC: 97433 AN: 151406 Hom.: 31736 Cov.: 33 AF XY: 0.652 AC XY: 48237 AN XY: 74034

African (AFR) AF: 0.532 AC: 21707 AN: 40810

American (AMR) AF: 0.615 AC: 9394 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2327 AN: 3470

East Asian (EAS) AF: 0.794 AC: 4106 AN: 5172

South Asian (SAS) AF: 0.831 AC: 4000 AN: 4814

European-Finnish (FIN) AF: 0.714 AC: 7564 AN: 10598

Middle Eastern (MID) AF: 0.807 AC: 234 AN: 290

European-Non Finnish (NFE) AF: 0.677 AC: 46047 AN: 67974

Other (OTH) AF: 0.669 AC: 1403 AN: 2098

Alfa AF: 0.543 Hom.: 1555

Bravo AF: 0.631

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.29
DANN	Benign	0.42
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4305276; hg19: chr2-241495013;