rs11153113

chr6-108435164-G-Achr6-108435164-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145315.5(AFG1L):c.808-12050G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 152,068 control chromosomes in the GnomAD database, including 10,177 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.

• Frequency: Genomes: 𝑓 0.36 (10177 hom., cov: 32)
• Consequence: AFG1L NM_145315.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AFG1L	NM_145315.5	c.808-12050G>A		intron_variant		ENST00000368977.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFG1L	ENST00000368977.9	c.808-12050G>A		intron_variant		1	NM_145315.5	P1
AFG1L	ENST00000421954.5	c.411-12050G>A		intron_variant		5
AFG1L	ENST00000431865.1	c.232-12050G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54636 AN: 151952 Hom.: 10177 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.359 AC: 54650 AN: 152068 Hom.: 10177 Cov.: 32 AF XY: 0.354 AC XY: 26330 AN XY: 74322

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.385

Alfa AF: 0.365 Hom.: 3542

Bravo AF: 0.354

Asia WGS AF: 0.248 AC: 863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.27
Dann	Benign	0.55

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: rs11153113; hg19: chr6-108756368;