18-49849562-C-G

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080467.3. 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
	MYO5B	NM_001080467.3	MANE Select	c.4315+5G>C		splice_region intron	N/A	NP_001073936.1	Q9ULV0-1
	SNHG22	NR_117096.1		n.193-75C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5B	ENST00000285039.12	TSL:1 MANE Select	c.4315+5G>C		splice_region intron	N/A	ENSP00000285039.6	Q9ULV0-1
	MYO5B	ENST00000592688.1	TSL:1	c.25+5G>C		splice_region intron	N/A	ENSP00000466368.1	Q9ULV0-3
	MYO5B	ENST00000697219.1		c.4048+5G>C		splice_region intron	N/A	ENSP00000513188.1	A0A8V8TM52

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Congenital microvillous atrophy (4)
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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;