6-30584276-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2 BP4_Strong BP6_Moderate BS1 BS2

The NM_001025091.2(ABCF1):c.1187G>A(p.Arg396Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000916 in 1,613,058 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0048 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00051 (4 hom.)
• Consequence: ABCF1 NM_001025091.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0470

Genes affected

ABCF1 (HGNC:70): (ATP binding cassette subfamily F member 1) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the GCN20 subfamily. Unlike other members of the superfamily, this protein lacks the transmembrane domains which are characteristic of most ABC transporters. This protein may be regulated by tumor necrosis factor-alpha and play a role in enhancement of protein synthesis and the inflammation process. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• PP2: Missense variant where missense usually causes diseases, ABCF1
• BP4: Computational evidence support a benign effect (MetaRNN=0.0049819946).
• BP6: Variant 6-30584276-G-A is Benign according to our data. Variant chr6-30584276-G-A is described in ClinVar as [Benign]. Clinvar id is 714311.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0048 (730/152232) while in subpopulation AFR AF= 0.0166 (689/41512). AF 95% confidence interval is 0.0156. There are 9 homozygotes in gnomad4. There are 316 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCF1	NM_001025091.2	c.1187G>A	p.Arg396Gln	missense_variant	13/25	ENST00000326195.13
ABCF1	NM_001090.3	c.1073G>A	p.Arg358Gln	missense_variant	12/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCF1	ENST00000326195.13	c.1187G>A	p.Arg396Gln	missense_variant	13/25	1	NM_001025091.2	A1
ABCF1	ENST00000376545.7	c.1073G>A	p.Arg358Gln	missense_variant	12/24	1
ABCF1	ENST00000475993.1	c.440G>A	p.Arg147Gln	missense_variant, NMD_transcript_variant	5/18	1
ABCF1	ENST00000441867.6	c.1190G>A	p.Arg397Gln	missense_variant	13/25	5		P3

Frequencies

GnomAD3 genomes AF: 0.00480 AC: 730 AN: 152114 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0166

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00125 AC: 309 AN: 246460 Hom.: 0 AF XY: 0.000864 AC XY: 116 AN XY: 134328

Gnomad AFR exome AF: 0.0170

Gnomad AMR exome AF: 0.000841

Gnomad ASJ exome AF: 0.000301

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000988

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000109

Gnomad OTH exome AF: 0.000988

GnomAD4 exome AF: 0.000511 AC: 747 AN: 1460826 Hom.: 4 Cov.: 32 AF XY: 0.000446 AC XY: 324 AN XY: 726728

Gnomad4 AFR exome AF: 0.0161

Gnomad4 AMR exome AF: 0.00112

Gnomad4 ASJ exome AF: 0.000306

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000710

Gnomad4 OTH exome AF: 0.000977

GnomAD4 genome AF: 0.00480 AC: 730 AN: 152232 Hom.: 9 Cov.: 32 AF XY: 0.00424 AC XY: 316 AN XY: 74444

Gnomad4 AFR AF: 0.0166

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.000947 Hom.: 2

Bravo AF: 0.00512

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0143 AC: 43

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00143 AC: 169

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

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

Invitae

Jul 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.33
Cadd	Benign	11
Dann	Benign	0.90
DEOGEN2	Benign	0.21	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.12	N
MetaRNN	Benign	0.0050	T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.37	N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.31	N;N
REVEL	Benign	0.17
Sift	Benign	0.50	T;T
Sift4G	Benign	0.40	T;T
Polyphen		0.17	B;.
Vest4		0.068
MVP		0.72
MPC		0.82
ClinPred		0.0014	T
GERP RS		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.056
gMVP		0.64

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: rs61741255; hg19: chr6-30552053;