Variant rs2274776 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_145315.5(AFG1L):c.1204-30A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 1,148,788 control chromosomes in the GnomAD database, including 125,025 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.52 ( 21828 hom., cov: 32)

Exomes 𝑓: 0.45 ( 103197 hom. )

Consequence

AFG1L
NM_145315.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.19

Variant links:

Genes affected

AFG1L (HGNC:16411): (AFG1 like ATPase) This gene encodes a mitochondrial integral membrane protein that plays a role in mitochondrial protein homeostasis. The protein contains a P-loop motif and a five-domain structure that is conserved in fly, yeast, and bacteria. It functions to mediate the degradation of nuclear-encoded complex IV subunits. Two conserved estrogen receptor binding sites are located within 2.5 kb of this gene. Polymorphisms in this gene have been associated with bipolar disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2016]

AFG1L links:

ENSG00000287044 (HGNC:):

ENSG00000287044 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFG1L	NM_145315.5 link	c.1204-30A>G		intron_variant	Intron 11 of 12	ENST00000368977.9	NP_660358.2	Q8WV93

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFG1L	ENST00000368977.9 link	c.1204-30A>G		intron_variant	Intron 11 of 12	1	NM_145315.5	ENSP00000357973.3		Q8WV93

Frequencies

GnomAD3 genomes

AF:

0.520

AC:

79023

AN:

151932

Hom.:

21802

Cov.:

show subpopulations

Gnomad AFR

AF:

0.721

Gnomad AMI

AF:

0.509

Gnomad AMR

AF:

0.431

Gnomad ASJ

AF:

0.400

Gnomad EAS

AF:

0.276

Gnomad SAS

AF:

0.419

Gnomad FIN

AF:

0.461

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.459

Gnomad OTH

AF:

0.506

GnomAD3 exomes

AF:

0.442

AC:

102037

AN:

230620

Hom.:

23826

AF XY:

0.440

AC XY:

54732

AN XY:

124492

show subpopulations

Gnomad AFR exome

AF:

0.731

Gnomad AMR exome

AF:

0.345

Gnomad ASJ exome

AF:

0.409

Gnomad EAS exome

AF:

0.271

Gnomad SAS exome

AF:

0.410

Gnomad FIN exome

AF:

0.464

Gnomad NFE exome

AF:

0.460

Gnomad OTH exome

AF:

0.441

GnomAD4 exome

AF:

0.448

AC:

446450

AN:

996738

Hom.:

103197

Cov.:

AF XY:

0.446

AC XY:

228895

AN XY:

513482

show subpopulations

Gnomad4 AFR exome

AF:

0.725

Gnomad4 AMR exome

AF:

0.357

Gnomad4 ASJ exome

AF:

0.406

Gnomad4 EAS exome

AF:

0.257

Gnomad4 SAS exome

AF:

0.406

Gnomad4 FIN exome

AF:

0.456

Gnomad4 NFE exome

AF:

0.458

Gnomad4 OTH exome

AF:

0.449

GnomAD4 genome

AF:

0.520

AC:

79089

AN:

152050

Hom.:

21828

Cov.:

AF XY:

0.515

AC XY:

38256

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.721

Gnomad4 AMR

AF:

0.430

Gnomad4 ASJ

AF:

0.400

Gnomad4 EAS

AF:

0.277

Gnomad4 SAS

AF:

0.420

Gnomad4 FIN

AF:

0.461

Gnomad4 NFE

AF:

0.459

Gnomad4 OTH

AF:

0.501

Alfa

AF:

0.468

Hom.:

19811

Bravo

AF:

0.527

Asia WGS

AF:

0.348

AC:

1212

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.022

DANN

Benign

0.34

BranchPoint Hunter

1.0

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over