rs253414

Variant names:

• chr5-75660692-C-T
• rs253414
• NM_001276713.2:c.1095+1311C>T

Variant summary

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

The NM_001276713.2(ANKDD1B):​c.1095+1311C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 152,040 control chromosomes in the GnomAD database, including 25,678 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 0.57 (25678 hom., cov: 32)
• Consequence: ANKDD1B NM_001276713.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.978
• Publications: 13 publications found

Genes affected

ANKDD1B (HGNC:32525): (ankyrin repeat and death domain containing 1B) Predicted to be involved in signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

ANKDD1B Gene-Disease associations (from GenCC):

• ankylosing spondylitis

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKDD1B	NM_001276713.2	c.1095+1311C>T		intron_variant	Intron 10 of 13	ENST00000601380.4	NP_001263642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKDD1B	ENST00000601380.4	c.1095+1311C>T		intron_variant	Intron 10 of 13	5	NM_001276713.2	ENSP00000471417.1

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86516 AN: 151918 Hom.: 25666 Cov.: 32

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.569 AC: 86566 AN: 152040 Hom.: 25678 Cov.: 32 AF XY: 0.563 AC XY: 41841 AN XY: 74334

African (AFR) AF: 0.412 AC: 17064 AN: 41446

American (AMR) AF: 0.613 AC: 9369 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 2020 AN: 3462

East Asian (EAS) AF: 0.376 AC: 1943 AN: 5174

South Asian (SAS) AF: 0.432 AC: 2079 AN: 4814

European-Finnish (FIN) AF: 0.621 AC: 6566 AN: 10566

Middle Eastern (MID) AF: 0.702 AC: 205 AN: 292

European-Non Finnish (NFE) AF: 0.669 AC: 45491 AN: 67976

Other (OTH) AF: 0.600 AC: 1267 AN: 2110

Alfa AF: 0.633 Hom.: 117200

Bravo AF: 0.567

Asia WGS AF: 0.415 AC: 1447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.24
DANN	Benign	0.56
PhyloP100		-0.98
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: rs253414; hg19: chr5-74956517;