chr12-69866584-G-A

Variant names:

• chr12-69866584-G-A
• rs11177914
• NM_182530.3:c.137+11214G>A

Variant summary

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

The NM_182530.3(MYRFL):​c.137+11214G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,090 control chromosomes in the GnomAD database, including 1,193 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 0.11 (1193 hom., cov: 32)
• Consequence: MYRFL NM_182530.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.366
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.161 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYRFL	NM_182530.3	MANE Select	c.137+11214G>A		intron	N/A	NP_872336.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYRFL	ENST00000552032.7	TSL:5 MANE Select	c.137+11214G>A		intron	N/A	ENSP00000448753.2
	MYRFL	ENST00000547771.6	TSL:5	c.137+11214G>A		intron	N/A	ENSP00000449598.2

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16246 AN: 151972 Hom.: 1192 Cov.: 32

Gnomad AFR AF: 0.0312

Gnomad AMI AF: 0.0956

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0363

Gnomad FIN AF: 0.0947

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.107 AC: 16243 AN: 152090 Hom.: 1193 Cov.: 32 AF XY: 0.102 AC XY: 7545 AN XY: 74324

African (AFR) AF: 0.0311 AC: 1290 AN: 41484

American (AMR) AF: 0.115 AC: 1753 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 521 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.0370 AC: 178 AN: 4814

European-Finnish (FIN) AF: 0.0947 AC: 1002 AN: 10578

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11106 AN: 67976

Other (OTH) AF: 0.120 AC: 253 AN: 2114

Alfa AF: 0.121 Hom.: 221

Bravo AF: 0.105

Asia WGS AF: 0.0250 AC: 88 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.8
DANN	Benign	0.71
PhyloP100		0.37
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: rs11177914; hg19: chr12-70260364;