5-140507254-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_017747.3(ANKHD1):c.3551+277A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 152,084 control chromosomes in the GnomAD database, including 34,539 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.67 (34539 hom., cov: 32)
• Consequence: ANKHD1 NM_017747.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.62

Genes affected

ANKHD1 (HGNC:24714): (ankyrin repeat and KH domain containing 1) This gene encodes a protein with multiple ankyrin repeat domains and a single KH-domain. The protein is thought to function as a scaffolding protein, and it may be involved in the regulation of caspases and thereby play an antiapoptotic role in cell survival. Alternative splicing results in multiple transcript variants, one of which generates a fusion transcript (MASK-BP3) with the downstream eIF4E-binding protein 3 (EIF4EBP3) gene, resulting in a protein comprised of the ANKHD1 sequence for the majority of the protein and a different C-terminus due to an alternate reading frame for the EIF4EBP3 segments. [provided by RefSeq, Sep 2010]

ANKHD1-EIF4EBP3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 5-140507254-A-G is Benign according to our data. Variant chr5-140507254-A-G is described in ClinVar as [Benign]. Clinvar id is 1228896.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKHD1	NM_017747.3	c.3551+277A>G		intron_variant		ENST00000360839.7
ANKHD1-EIF4EBP3	NM_020690.6	c.3551+277A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKHD1	ENST00000360839.7	c.3551+277A>G		intron_variant		1	NM_017747.3	P1

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101739 AN: 151966 Hom.: 34520 Cov.: 32

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.841

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.681

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

GnomAD4 genome AF: 0.669 AC: 101815 AN: 152084 Hom.: 34539 Cov.: 32 AF XY: 0.668 AC XY: 49633 AN XY: 74340

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.694

Gnomad4 ASJ AF: 0.660

Gnomad4 EAS AF: 0.841

Gnomad4 SAS AF: 0.752

Gnomad4 FIN AF: 0.636

Gnomad4 NFE AF: 0.700

Gnomad4 OTH AF: 0.682

Alfa AF: 0.650 Hom.: 5192

Bravo AF: 0.671

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 21, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.087
Dann	Benign	0.27

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

Publications

LitVar

Other links and lift over

dbSNP: rs6871703; hg19: chr5-139886839; COSMIC: COSV51843617; COSMIC: COSV51843617;