rs2072783

Variant names:

• chr6-16143666-A-G
• rs2072783
• NM_013262.4:c.663-33A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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
• Publications: 15 publications found

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

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

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 3 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013262.4. 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
	MYLIP	NM_013262.4	MANE Select	c.663-33A>G		intron	N/A	NP_037394.2
	MYLIP	NM_001436627.1		c.662+449A>G		intron	N/A	NP_001423556.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYLIP	ENST00000356840.8	TSL:1 MANE Select	c.663-33A>G		intron	N/A	ENSP00000349298.3
	MYLIP	ENST00000349606.5	TSL:1	n.*247-33A>G		intron	N/A	ENSP00000008686.6
	MYLIP	ENST00000718320.1		c.663-33A>G		intron	N/A	ENSP00000520754.1

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

GnomAD2 exomes AF: 0.174 AC: 43245 AN: 248754 AF XY: 0.170

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 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

African (AFR) AF: 0.0583 AC: 1946 AN: 33364

American (AMR) AF: 0.270 AC: 11983 AN: 44442

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 3523 AN: 25872

East Asian (EAS) AF: 0.399 AC: 15817 AN: 39636

South Asian (SAS) AF: 0.190 AC: 16267 AN: 85790

European-Finnish (FIN) AF: 0.161 AC: 8545 AN: 53190

Middle Eastern (MID) AF: 0.0881 AC: 504 AN: 5720

European-Non Finnish (NFE) AF: 0.120 AC: 133302 AN: 1108842

Other (OTH) AF: 0.143 AC: 8597 AN: 60206

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

African (AFR) AF: 0.0654 AC: 2715 AN: 41520

American (AMR) AF: 0.185 AC: 2830 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 486 AN: 3470

East Asian (EAS) AF: 0.410 AC: 2119 AN: 5168

South Asian (SAS) AF: 0.203 AC: 978 AN: 4826

European-Finnish (FIN) AF: 0.162 AC: 1715 AN: 10566

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8446 AN: 67986

Other (OTH) AF: 0.136 AC: 288 AN: 2114

Alfa AF: 0.131 Hom.: 1013

Bravo AF: 0.132

Asia WGS AF: 0.306 AC: 1065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.7
DANN	Benign	0.63
PhyloP100		0.88
BranchPoint Hunter		3.0
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: rs2072783; hg19: chr6-16143897; COSMIC: COSV62766336; COSMIC: COSV62766336;