Variant chr7-151218772-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_007189.3(ABCF2):c.1119G>C(p.Glu373Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ABCF2
NM_007189.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.120

Variant links:

Genes affected

ABCF2 (HGNC:71): (ATP binding cassette subfamily F member 2) This gene encodes a member of the ATP-binding cassette (ABC) transporter superfamily. ATP-binding cassette proteins transport various molecules across extra- and intracellular membranes. Alterations in this gene may be involved in cancer progression. Related pseudogenes have been identified on chromosomes 3 and 7. [provided by RefSeq, Mar 2019]

ABCF2 links:

ABCF2-H2BK1 (HGNC:):

ABCF2-H2BK1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2

Missense variant where missense usually causes diseases, ABCF2

BP4

Computational evidence support a benign effect (MetaRNN=0.25766963).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ABCF2	NM_007189.3 linkuse as main transcript	c.1119G>C	p.Glu373Asp	missense_variant	9/15	ENST00000287844.7
ABCF2-H2BK1	NR_160983.1 linkuse as main transcript	n.1204G>C		non_coding_transcript_exon_variant	9/17
ABCF2-H2BK1	NM_005692.5 linkuse as main transcript	c.1119G>C	p.Glu373Asp	missense_variant	9/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCF2	ENST00000287844.7 linkuse as main transcript	c.1119G>C	p.Glu373Asp	missense_variant	9/15	1	NM_007189.3	P1	Q9UG63-1
ABCF2	ENST00000473874.1 linkuse as main transcript	n.508G>C		non_coding_transcript_exon_variant	4/6	3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151870

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151870

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74146

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 20, 2023

The c.1119G>C (p.E373D) alteration is located in exon 9 (coding exon 8) of the ABCF2 gene. This alteration results from a G to C substitution at nucleotide position 1119, causing the glutamic acid (E) at amino acid position 373 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.050

MetaRNN

Benign

0.26

T;T

MetaSVM

Uncertain

-0.23

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-2.1

N;N

REVEL

Uncertain

0.33

Sift

Benign

0.083

T;T

Sift4G

Benign

0.14

T;T

Polyphen

0.029

.;B

Vest4

0.40

MutPred

0.30

Loss of helix (P = 0.079);Loss of helix (P = 0.079);

MVP

0.70

MPC

0.66

ClinPred

0.44

GERP RS

-0.95

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over