rs12053254

Variant names:

• chr2-189742427-T-C
• rs12053254
• NM_001378068.1:c.3811-848T>C

Variant summary

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

The NM_001378068.1(ANKAR):​c.3811-848T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0804 in 152,170 control chromosomes in the GnomAD database, including 623 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 0.080 (623 hom., cov: 32)
• Consequence: ANKAR NM_001378068.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.832
• Publications: 11 publications found

Genes affected

ANKAR (HGNC:26350): (ankyrin and armadillo repeat containing) Predicted to be integral component of membrane. [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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKAR	NM_001378068.1	c.3811-848T>C		intron_variant	Intron 20 of 22	ENST00000684021.1	NP_001364997.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKAR	ENST00000684021.1	c.3811-848T>C		intron_variant	Intron 20 of 22		NM_001378068.1	ENSP00000507233.1

Frequencies

GnomAD3 genomes AF: 0.0805 AC: 12236 AN: 152052 Hom.: 623 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.0401

Gnomad FIN AF: 0.0801

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0477

Gnomad OTH AF: 0.0645

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

GnomAD4 genome AF: 0.0804 AC: 12240 AN: 152170 Hom.: 623 Cov.: 32 AF XY: 0.0810 AC XY: 6027 AN XY: 74390

African (AFR) AF: 0.129 AC: 5333 AN: 41498

American (AMR) AF: 0.111 AC: 1691 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0205 AC: 71 AN: 3468

East Asian (EAS) AF: 0.133 AC: 689 AN: 5174

South Asian (SAS) AF: 0.0393 AC: 190 AN: 4830

European-Finnish (FIN) AF: 0.0801 AC: 848 AN: 10588

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0477 AC: 3241 AN: 68002

Other (OTH) AF: 0.0648 AC: 137 AN: 2114

Alfa AF: 0.0634 Hom.: 1099

Bravo AF: 0.0862

Asia WGS AF: 0.0770 AC: 268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.1
DANN	Benign	0.83
PhyloP100		-0.83
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: rs12053254; hg19: chr2-190607153;