5-75611640-C-G

Variant names:

• chr5-75611640-C-G
• rs114367272
• NM_001276713.2:c.6C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001276713.2(ANKDD1B):​c.6C>G​(p.Asp2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00258 in 1,231,354 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (39 hom., cov: 31)
  • Exomes 𝑓: 0.0012 (35 hom.)
• Consequence: ANKDD1B NM_001276713.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.920
• Publications: 0 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034317076).
• BP6: Variant 5-75611640-C-G is Benign according to our data. Variant chr5-75611640-C-G is described in ClinVar as Benign. ClinVar VariationId is 776047.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0123 (1870/152032) while in subpopulation AFR AF = 0.0429 (1777/41426). AF 95% confidence interval is 0.0412. There are 39 homozygotes in GnomAd4. There are 910 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1870 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001276713.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKDD1B	NM_001276713.2	MANE Select	c.6C>G	p.Asp2Glu	missense	Exon 1 of 14	NP_001263642.1	A6NHY2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKDD1B	ENST00000601380.4	TSL:5 MANE Select	c.6C>G	p.Asp2Glu	missense	Exon 1 of 14	ENSP00000471417.1	A6NHY2
	ANKDD1B	ENST00000885189.1		c.6C>G	p.Asp2Glu	missense	Exon 1 of 14	ENSP00000555248.1
	ANKDD1B	ENST00000885191.1		c.6C>G	p.Asp2Glu	missense	Exon 1 of 12	ENSP00000555250.1

Frequencies

GnomAD3 genomes AF: 0.0123 AC: 1865 AN: 151914 Hom.: 40 Cov.: 31

Gnomad AFR AF: 0.0429

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00 AC: 0 AN: 136 AF XY: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00121 AC: 1307 AN: 1079322 Hom.: 35 Cov.: 30 AF XY: 0.00113 AC XY: 576 AN XY: 509634

African (AFR) AF: 0.0461 AC: 1057 AN: 22934

American (AMR) AF: 0.00333 AC: 28 AN: 8402

Ashkenazi Jewish (ASJ) AF: 0.00278 AC: 40 AN: 14364

East Asian (EAS) AF: 0.00 AC: 0 AN: 26516

South Asian (SAS) AF: 0.000103 AC: 2 AN: 19490

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21108

Middle Eastern (MID) AF: 0.00309 AC: 9 AN: 2914

European-Non Finnish (NFE) AF: 0.0000391 AC: 36 AN: 919952

Other (OTH) AF: 0.00309 AC: 135 AN: 43642

GnomAD4 genome AF: 0.0123 AC: 1870 AN: 152032 Hom.: 39 Cov.: 31 AF XY: 0.0122 AC XY: 910 AN XY: 74338

African (AFR) AF: 0.0429 AC: 1777 AN: 41426

American (AMR) AF: 0.00386 AC: 59 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67964

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.00197 Hom.: 1

Bravo AF: 0.0145

ExAC AF: 0.000289 AC: 1

Asia WGS AF: 0.00318 AC: 13 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.53
DANN	Benign	0.64
DEOGEN2	Benign	0.0045	T
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.19	T
MetaRNN	Benign	0.0034	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.92
PrimateAI	Uncertain	0.69	T
Sift4G	Pathogenic	0.0	D
Vest4		0.039
MVP		0.34
GERP RS		-0.055
PromoterAI		0.072	Neutral
Varity_R		0.036
gMVP		0.042
Mutation Taster		=99/1	polymorphism

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: rs114367272; hg19: chr5-74907465;