chr7-151223986-C-T

Position:

chr7-151223986-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_007189.3(ABCF2):c.496G>A(p.Asp166Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000855 in 1,614,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000089 ( 0 hom. )

Consequence

ABCF2
NM_007189.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.63

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:54751): (ABCF2-H2BK1 readthrough) This gene represents readthrough transcription between ABCF2 and a downstream histone H2B-like gene. [provided by RefSeq, Mar 2019]

ABCF2-H2BK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.832

BS2

High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCF2	NM_007189.3 link	c.496G>A	p.Asp166Asn	missense_variant	4/15	ENST00000287844.7	NP_009120.1	Q9UG63-1A0A090N7X1
ABCF2-H2BK1	NM_005692.5 link	c.496G>A	p.Asp166Asn	missense_variant	4/16		NP_005683.2	Q9UG63-2A0A090N7Y2
ABCF2-H2BK1	NR_160983.1 link	n.581G>A		non_coding_transcript_exon_variant	4/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ABCF2	ENST00000287844.7 link	c.496G>A	p.Asp166Asn	missense_variant	4/15	1	NM_007189.3	ENSP00000287844.2	Q9UG63-1
ABCF2-H2BK1	ENST00000222388.6 link	c.496G>A	p.Asp166Asn	missense_variant	4/16	5		ENSP00000222388.2
ABCF2	ENST00000468073.5 link	c.496G>A	p.Asp166Asn	missense_variant	3/6	2		ENSP00000419720.1	C9JZV3
ABCF2	ENST00000441774.1 link	c.496G>A	p.Asp166Asn	missense_variant	4/5	3		ENSP00000395785.1	C9JHK9

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251216

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000792

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000889

AC:

130

AN:

1461812

Hom.:

Cov.:

AF XY:

0.0000866

AC XY:

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000112

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000264

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.0000545

EpiControl

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

Dec 03, 2024

The c.496G>A (p.D166N) alteration is located in exon 4 (coding exon 3) of the ABCF2 gene. This alteration results from a G to A substitution at nucleotide position 496, causing the aspartic acid (D) at amino acid position 166 to be replaced by an asparagine (N). 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

Pathogenic

0.89

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.60

.;D;.;.

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

D;D;D;D

M_CAP

Uncertain

0.14

MetaRNN

Pathogenic

0.83

D;D;D;D

MetaSVM

Uncertain

0.78

MutationAssessor

Benign

1.5

.;L;.;.

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-4.2

D;D;D;D

REVEL

Uncertain

0.38

Sift

Benign

0.051

T;T;D;D

Sift4G

Benign

0.15

T;T;.;T

Polyphen

0.99

.;D;.;.

Vest4

0.94

MutPred

0.77

Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);

MVP

0.85

MPC

0.84

ClinPred

0.51

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.29

gMVP

0.78

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

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