rs11177914

Positions:

• chr12-69866584-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYRFL	NM_182530.3	c.137+11214G>A		intron_variant		ENST00000552032.7	NP_872336.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYRFL	ENST00000552032.7	c.137+11214G>A		intron_variant		5	NM_182530.3	ENSP00000448753.2
MYRFL	ENST00000547771.6	c.137+11214G>A		intron_variant		5		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

Gnomad4 AFR AF: 0.0311

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0370

Gnomad4 FIN AF: 0.0947

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.120

Alfa AF: 0.123 Hom.: 219

Bravo AF: 0.105

Asia WGS AF: 0.0250 AC: 88 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.8
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs11177914; hg19: chr12-70260364;