NM_012307.5:c.2122-104G>A

Variant names:

• chr18-5407840-C-T
• rs2874686
• NM_012307.5:c.2122-104G>A

Variant summary

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

The NM_012307.5(EPB41L3):​c.2122-104G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 1,000,310 control chromosomes in the GnomAD database, including 387,296 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 0.72 (46144 hom., cov: 34)
  • Exomes 𝑓: 0.89 (341152 hom.)
• Consequence: EPB41L3 NM_012307.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.740
• Publications: 10 publications found

Genes affected

EPB41L3 (HGNC:3380): (erythrocyte membrane protein band 4.1 like 3) Predicted to enable cytoskeletal protein-membrane anchor activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in several processes, including nervous system development; paranodal junction maintenance; and protein localization to paranode region of axon. Located in cell-cell junction and plasma membrane. Biomarker of meningioma. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPB41L3	NM_012307.5	c.2122-104G>A		intron_variant	Intron 14 of 22	ENST00000341928.7	NP_036439.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPB41L3	ENST00000341928.7	c.2122-104G>A		intron_variant	Intron 14 of 22	1	NM_012307.5	ENSP00000343158.2

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109945 AN: 152092 Hom.: 46145 Cov.: 34

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.851

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.939

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.918

Gnomad OTH AF: 0.760

GnomAD4 exome AF: 0.890 AC: 754668 AN: 848100 Hom.: 341152 AF XY: 0.890 AC XY: 396165 AN XY: 445286

African (AFR) AF: 0.248 AC: 5055 AN: 20402

American (AMR) AF: 0.844 AC: 33850 AN: 40112

Ashkenazi Jewish (ASJ) AF: 0.902 AC: 19023 AN: 21096

East Asian (EAS) AF: 0.909 AC: 33482 AN: 36836

South Asian (SAS) AF: 0.808 AC: 56454 AN: 69910

European-Finnish (FIN) AF: 0.945 AC: 49449 AN: 52352

Middle Eastern (MID) AF: 0.824 AC: 3731 AN: 4528

European-Non Finnish (NFE) AF: 0.923 AC: 519580 AN: 563026

Other (OTH) AF: 0.855 AC: 34044 AN: 39838

GnomAD4 genome AF: 0.722 AC: 109952 AN: 152210 Hom.: 46144 Cov.: 34 AF XY: 0.726 AC XY: 54000 AN XY: 74416

African (AFR) AF: 0.258 AC: 10693 AN: 41450

American (AMR) AF: 0.814 AC: 12455 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 3149 AN: 3470

East Asian (EAS) AF: 0.916 AC: 4751 AN: 5186

South Asian (SAS) AF: 0.801 AC: 3867 AN: 4830

European-Finnish (FIN) AF: 0.939 AC: 9965 AN: 10616

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.918 AC: 62451 AN: 68032

Other (OTH) AF: 0.763 AC: 1613 AN: 2114

Alfa AF: 0.857 Hom.: 171851

Bravo AF: 0.693

Asia WGS AF: 0.803 AC: 2791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.057
DANN	Benign	0.63
PhyloP100		-0.74
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: rs2874686; hg19: chr18-5407839;