chr15-45406595-T-G

Variant names:

• chr15-45406595-T-G
• rs2467853
• NM_024063.3:c.1275+1090T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024063.3(AFG2B):​c.1275+1090T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 152,044 control chromosomes in the GnomAD database, including 27,396 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 0.56 (27396 hom., cov: 32)
• Consequence: AFG2B NM_024063.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480
• Publications: 53 publications found

Genes affected

AFG2B (HGNC:28762): (AFG2 AAA ATPase homolog B) Predicted to enable ATP binding activity. Located in cytoplasm and spindle. [provided by Alliance of Genome Resources, Apr 2022]

AFG2B Gene-Disease associations (from GenCC):

• hearing loss, autosomal recessive 119

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• neurodevelopmental disorder with hearing loss and spasticity

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFG2B	NM_024063.3	c.1275+1090T>G		intron_variant	Intron 2 of 7	ENST00000305560.11	NP_076968.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AFG2B	ENST00000305560.11	c.1275+1090T>G		intron_variant	Intron 2 of 7	1	NM_024063.3	ENSP00000305494.6
AFG2B	ENST00000525552.1	n.46-434T>G		intron_variant	Intron 1 of 2	3		ENSP00000453091.1
AFG2B	ENST00000531970.5	n.1275+1090T>G		intron_variant	Intron 2 of 7	2		ENSP00000436823.1
AFG2B	ENST00000559860.2	n.1335+1090T>G		intron_variant	Intron 2 of 4	2

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85151 AN: 151926 Hom.: 27337 Cov.: 32

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.908

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.561 AC: 85274 AN: 152044 Hom.: 27396 Cov.: 32 AF XY: 0.567 AC XY: 42159 AN XY: 74304

African (AFR) AF: 0.842 AC: 34925 AN: 41484

American (AMR) AF: 0.620 AC: 9483 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1848 AN: 3470

East Asian (EAS) AF: 0.908 AC: 4705 AN: 5182

South Asian (SAS) AF: 0.593 AC: 2862 AN: 4824

European-Finnish (FIN) AF: 0.408 AC: 4291 AN: 10524

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25597 AN: 67958

Other (OTH) AF: 0.562 AC: 1186 AN: 2112

Alfa AF: 0.462 Hom.: 10856

Bravo AF: 0.592

Asia WGS AF: 0.737 AC: 2548 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	6.7
DANN	Benign	0.77
PhyloP100		-0.48
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: rs2467853; hg19: chr15-45698793;