ENST00000592688.1:c.-142G>C

Variant names:

• chr18-49849733-C-G
• rs490648
• ENST00000592688.1:c.-142G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000592688.1(MYO5B):​c.-142G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,224,514 control chromosomes in the GnomAD database, including 125,690 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15377 hom., cov: 33)
  • Exomes 𝑓: 0.44 (110313 hom.)
• Consequence: MYO5B ENST00000592688.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.271
• Publications: 10 publications found

Genes affected

MYO5B (HGNC:7603): (myosin VB) The protein encoded by this gene, together with other proteins, may be involved in plasma membrane recycling. Mutations in this gene are associated with microvillous inclusion disease. [provided by RefSeq, Sep 2009]

SNHG22 (HGNC:50285): (small nucleolar RNA host gene 22)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 18-49849733-C-G is Benign according to our data. Variant chr18-49849733-C-G is described in ClinVar as Benign. ClinVar VariationId is 1246653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000592688.1. 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
	MYO5B	NM_001080467.3	MANE Select	c.4222-73G>C		intron	N/A	NP_001073936.1
	SNHG22	NR_117096.1		n.289C>G		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5B	ENST00000592688.1	TSL:1	c.-142G>C		5_prime_UTR	Exon 1 of 9	ENSP00000466368.1
	MYO5B	ENST00000285039.12	TSL:1 MANE Select	c.4222-73G>C		intron	N/A	ENSP00000285039.6
	SNHG22	ENST00000589499.1	TSL:2	n.289C>G		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.441 AC: 67076 AN: 151974 Hom.: 15380 Cov.: 33

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.478

GnomAD4 exome AF: 0.444 AC: 475947 AN: 1072422 Hom.: 110313 Cov.: 14 AF XY: 0.443 AC XY: 244775 AN XY: 552234

African (AFR) AF: 0.435 AC: 11308 AN: 25994

American (AMR) AF: 0.269 AC: 11885 AN: 44172

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 13102 AN: 23678

East Asian (EAS) AF: 0.122 AC: 4632 AN: 37978

South Asian (SAS) AF: 0.330 AC: 25950 AN: 78574

European-Finnish (FIN) AF: 0.384 AC: 16996 AN: 44204

Middle Eastern (MID) AF: 0.483 AC: 2341 AN: 4842

European-Non Finnish (NFE) AF: 0.482 AC: 368834 AN: 765300

Other (OTH) AF: 0.438 AC: 20899 AN: 47680

GnomAD4 genome AF: 0.441 AC: 67086 AN: 152092 Hom.: 15377 Cov.: 33 AF XY: 0.433 AC XY: 32228 AN XY: 74354

African (AFR) AF: 0.434 AC: 18010 AN: 41466

American (AMR) AF: 0.372 AC: 5684 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1920 AN: 3470

East Asian (EAS) AF: 0.116 AC: 599 AN: 5166

South Asian (SAS) AF: 0.313 AC: 1512 AN: 4826

European-Finnish (FIN) AF: 0.396 AC: 4187 AN: 10576

Middle Eastern (MID) AF: 0.551 AC: 161 AN: 292

European-Non Finnish (NFE) AF: 0.491 AC: 33406 AN: 67980

Other (OTH) AF: 0.474 AC: 1002 AN: 2112

Alfa AF: 0.315 Hom.: 776

Bravo AF: 0.439

Asia WGS AF: 0.260 AC: 907 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.33
PhyloP100		-0.27
PromoterAI		0.019	Neutral
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: rs490648; hg19: chr18-47376103; COSMIC: COSV53217494;