5-75669267-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001276713.2(ANKDD1B):c.1409G>A(p.Arg470His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00638 in 1,232,134 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0039 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0067 (27 hom.)
• Consequence: ANKDD1B NM_001276713.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.33

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006200969).
• BP6: Variant 5-75669267-G-A is Benign according to our data. Variant chr5-75669267-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 719096.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKDD1B	NM_001276713.2	c.1409G>A	p.Arg470His	missense_variant	13/14	ENST00000601380.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKDD1B	ENST00000601380.4	c.1409G>A	p.Arg470His	missense_variant	13/14	5	NM_001276713.2	P1

Frequencies

GnomAD3 genomes AF: 0.00386 AC: 588 AN: 152210 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00629

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00583 AC: 49 AN: 8400 Hom.: 0 AF XY: 0.00520 AC XY: 21 AN XY: 4038

Gnomad AFR exome AF: 0.00286

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0211

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00320

Gnomad NFE exome AF: 0.00670

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00673 AC: 7268 AN: 1079806 Hom.: 27 Cov.: 28 AF XY: 0.00668 AC XY: 3407 AN XY: 509776

Gnomad4 AFR exome AF: 0.000697

Gnomad4 AMR exome AF: 0.00190

Gnomad4 ASJ exome AF: 0.00577

Gnomad4 EAS exome AF: 0.0000377

Gnomad4 SAS exome AF: 0.00231

Gnomad4 FIN exome AF: 0.00209

Gnomad4 NFE exome AF: 0.00739

Gnomad4 OTH exome AF: 0.00609

GnomAD4 genome AF: 0.00385 AC: 587 AN: 152328 Hom.: 2 Cov.: 32 AF XY: 0.00362 AC XY: 270 AN XY: 74492

Gnomad4 AFR AF: 0.00171

Gnomad4 AMR AF: 0.00320

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.000847

Gnomad4 NFE AF: 0.00628

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00485 Hom.: 0

Bravo AF: 0.00399

TwinsUK AF: 0.00701 AC: 26

ALSPAC AF: 0.00727 AC: 28

ExAC AF: 0.00190 AC: 20

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2023	ANKDD1B: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 03, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.22
Cadd	Benign	19
Dann	Benign	0.77
DEOGEN2	Benign	0.060	T
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.0062	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.26	T
Sift4G	Benign	0.13	T
Vest4		0.078
MVP		0.75
GERP RS		0.36
Varity_R		0.042
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs139309851; hg19: chr5-74965092;