rs11153113

Variant names:

• chr6-108435164-G-A
• rs11153113
• NM_145315.5:c.808-12050G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-108435164-G-A
• chr6-108435164-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145315.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFG1L	NM_145315.5	MANE Select	c.808-12050G>A		intron	N/A	NP_660358.2
	AFG1L	NM_001323005.2		c.808-12050G>A		intron	N/A	NP_001309934.1
	AFG1L	NR_136553.2		n.397-12050G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFG1L	ENST00000368977.9	TSL:1 MANE Select	c.808-12050G>A		intron	N/A	ENSP00000357973.3
	AFG1L	ENST00000908138.1		c.859-12050G>A		intron	N/A	ENSP00000578197.1
	AFG1L	ENST00000908137.1		c.802-12050G>A		intron	N/A	ENSP00000578196.1

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

African (AFR) AF: 0.274 AC: 11369 AN: 41496

American (AMR) AF: 0.340 AC: 5199 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1133 AN: 3470

East Asian (EAS) AF: 0.211 AC: 1094 AN: 5178

South Asian (SAS) AF: 0.303 AC: 1459 AN: 4822

European-Finnish (FIN) AF: 0.392 AC: 4133 AN: 10554

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28836 AN: 67968

Other (OTH) AF: 0.385 AC: 812 AN: 2108

Alfa AF: 0.364 Hom.: 3574

Bravo AF: 0.354

Asia WGS AF: 0.248 AC: 863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.27
DANN	Benign	0.55
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11153113; hg19: chr6-108756368;