12-69869791-T-C

Variant names:

• chr12-69869791-T-C
• rs1240224
• NM_182530.3:c.138-9237T>C

Variant summary

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

The NM_182530.3(MYRFL):​c.138-9237T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 151,984 control chromosomes in the GnomAD database, including 29,728 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 0.61 (29728 hom., cov: 31)
• Consequence: MYRFL NM_182530.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 6 publications found

Genes affected

MYRFL (HGNC:26316): (myelin regulatory factor like) Predicted to enable DNA-binding transcription factor activity and sequence-specific DNA binding activity. Predicted to be involved in positive regulation of transcription, DNA-templated and protein autoprocessing. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum membrane and nucleus. [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 = 0.69 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182530.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYRFL	NM_182530.3	MANE Select	c.138-9237T>C		intron	N/A	NP_872336.2	Q96LU7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYRFL	ENST00000552032.7	TSL:5 MANE Select	c.138-9237T>C		intron	N/A	ENSP00000448753.2	Q96LU7
	MYRFL	ENST00000535034.6	TSL:1	c.138-9237T>C		intron	N/A	ENSP00000440626.2
	MYRFL	ENST00000547771.6	TSL:5	c.138-9237T>C		intron	N/A	ENSP00000449598.2	F8VVR8

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93168 AN: 151864 Hom.: 29721 Cov.: 31

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.622

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

GnomAD4 genome AF: 0.613 AC: 93201 AN: 151984 Hom.: 29728 Cov.: 31 AF XY: 0.616 AC XY: 45780 AN XY: 74282

African (AFR) AF: 0.434 AC: 17967 AN: 41434

American (AMR) AF: 0.628 AC: 9596 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2385 AN: 3470

East Asian (EAS) AF: 0.521 AC: 2681 AN: 5142

South Asian (SAS) AF: 0.645 AC: 3103 AN: 4812

European-Finnish (FIN) AF: 0.761 AC: 8043 AN: 10570

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47224 AN: 67966

Other (OTH) AF: 0.616 AC: 1299 AN: 2108

Alfa AF: 0.671 Hom.: 17883

Bravo AF: 0.595

Asia WGS AF: 0.570 AC: 1979 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.64
DANN	Benign	0.40
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: rs1240224; hg19: chr12-70263571;