rs2072783

Positions:

• chr6-16143666-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_013262.4(MYLIP):​c.663-33A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,609,184 control chromosomes in the GnomAD database, including 18,166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.13 (1702 hom., cov: 32)
  • Exomes 𝑓: 0.14 (16464 hom.)
• Consequence: MYLIP NM_013262.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.877

Genes affected

MYLIP (HGNC:21155): (myosin regulatory light chain interacting protein) The ERM protein family members ezrin, radixin, and moesin are cytoskeletal effector proteins linking actin to membrane-bound proteins at the cell surface. Myosin regulatory light chain interacting protein (MYLIP) is a novel ERM-like protein that interacts with myosin regulatory light chain and inhibits neurite outgrowth. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: This place is a probable branch point but likely benign (scored 3 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 6-16143666-A-G is Benign according to our data. Variant chr6-16143666-A-G is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYLIP	NM_013262.4	c.663-33A>G		intron_variant		ENST00000356840.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYLIP	ENST00000356840.8	c.663-33A>G		intron_variant		1	NM_013262.4	P1
MYLIP	ENST00000349606.4	c.120-33A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19783 AN: 152004 Hom.: 1698 Cov.: 32

Gnomad AFR AF: 0.0655

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.133

GnomAD3 exomes AF: 0.174 AC: 43245 AN: 248754 Hom.: 4767 AF XY: 0.170 AC XY: 22917 AN XY: 134412

Gnomad AFR exome AF: 0.0616

Gnomad AMR exome AF: 0.279

Gnomad ASJ exome AF: 0.141

Gnomad EAS exome AF: 0.399

Gnomad SAS exome AF: 0.192

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.123

Gnomad OTH exome AF: 0.158

GnomAD4 exome AF: 0.138 AC: 200484 AN: 1457062 Hom.: 16464 Cov.: 30 AF XY: 0.139 AC XY: 100528 AN XY: 724566

Gnomad4 AFR exome AF: 0.0583

Gnomad4 AMR exome AF: 0.270

Gnomad4 ASJ exome AF: 0.136

Gnomad4 EAS exome AF: 0.399

Gnomad4 SAS exome AF: 0.190

Gnomad4 FIN exome AF: 0.161

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.130 AC: 19797 AN: 152122 Hom.: 1702 Cov.: 32 AF XY: 0.134 AC XY: 9970 AN XY: 74352

Gnomad4 AFR AF: 0.0654

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.136

Alfa AF: 0.131 Hom.: 551

Bravo AF: 0.132

Asia WGS AF: 0.306 AC: 1065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.7
DANN	Benign	0.63
BranchPoint Hunter		3.0

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: rs2072783; hg19: chr6-16143897; COSMIC: COSV62766336; COSMIC: COSV62766336;