NM_001080467.3:c.4315+5G>C

Variant names:

• chr18-49849562-C-G
• rs488890
• NM_001080467.3:c.4315+5G>C

Variant summary

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

The NM_001080467.3(MYO5B):​c.4315+5G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 1,599,336 control chromosomes in the GnomAD database, including 171,694 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15407 hom., cov: 32)
  • Exomes 𝑓: 0.46 (156287 hom.)
• Consequence: MYO5B NM_001080467.3 splice_region, intron
• Scores: Splicing: ADA: 0.09528
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -4.32
• Publications: 15 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=-0.91).
• BP6: Variant 18-49849562-C-G is Benign according to our data. Variant chr18-49849562-C-G is described in ClinVar as Benign. ClinVar VariationId is 327014.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5B	NM_001080467.3	c.4315+5G>C		splice_region_variant, intron_variant	Intron 32 of 39	ENST00000285039.12	NP_001073936.1
SNHG22	NR_117096.1	n.193-75C>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5B	ENST00000285039.12	c.4315+5G>C		splice_region_variant, intron_variant	Intron 32 of 39	1	NM_001080467.3	ENSP00000285039.6

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67179 AN: 151942 Hom.: 15410 Cov.: 32

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.478

GnomAD2 exomes AF: 0.402 AC: 100225 AN: 249532 AF XY: 0.409

Gnomad AFR exome AF: 0.440

Gnomad AMR exome AF: 0.256

Gnomad ASJ exome AF: 0.549

Gnomad EAS exome AF: 0.114

Gnomad FIN exome AF: 0.392

Gnomad NFE exome AF: 0.491

Gnomad OTH exome AF: 0.436

GnomAD4 exome AF: 0.456 AC: 660342 AN: 1447276 Hom.: 156287 Cov.: 30 AF XY: 0.455 AC XY: 327787 AN XY: 720826

African (AFR) AF: 0.442 AC: 14686 AN: 33206

American (AMR) AF: 0.270 AC: 12092 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 14399 AN: 26052

East Asian (EAS) AF: 0.122 AC: 4854 AN: 39664

South Asian (SAS) AF: 0.334 AC: 28682 AN: 85962

European-Finnish (FIN) AF: 0.390 AC: 20813 AN: 53360

Middle Eastern (MID) AF: 0.503 AC: 2203 AN: 4378

European-Non Finnish (NFE) AF: 0.487 AC: 536106 AN: 1100158

Other (OTH) AF: 0.443 AC: 26507 AN: 59790

GnomAD4 genome AF: 0.442 AC: 67189 AN: 152060 Hom.: 15407 Cov.: 32 AF XY: 0.434 AC XY: 32271 AN XY: 74312

African (AFR) AF: 0.437 AC: 18113 AN: 41480

American (AMR) AF: 0.372 AC: 5683 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1921 AN: 3470

East Asian (EAS) AF: 0.116 AC: 599 AN: 5174

South Asian (SAS) AF: 0.314 AC: 1511 AN: 4816

European-Finnish (FIN) AF: 0.396 AC: 4183 AN: 10566

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.492 AC: 33415 AN: 67962

Other (OTH) AF: 0.474 AC: 999 AN: 2108

Alfa AF: 0.450 Hom.: 4598

Bravo AF: 0.440

Asia WGS AF: 0.260 AC: 905 AN: 3478

EpiCase AF: 0.502

EpiControl AF: 0.510

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Congenital microvillous atrophy Benign:4

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.037
DANN	Benign	0.46
PhyloP100		-4.3
PromoterAI		-0.070	Neutral
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.095
dbscSNV1_RF	Benign	0.11
SpliceAI score (max)		0.16		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: rs488890; hg19: chr18-47375932; COSMIC: COSV53217485;