18-49843388-C-T

Variant names:

• chr18-49843388-C-T
• rs2276170
• NM_001080467.3:c.4464G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001080467.3(MYO5B):​c.4464G>A​(p.Leu1488Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0731 in 1,613,966 control chromosomes in the GnomAD database, including 9,304 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.079 (950 hom., cov: 33)
  • Exomes 𝑓: 0.072 (8354 hom.)
• Consequence: MYO5B NM_001080467.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.750
• Publications: 14 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 18-49843388-C-T is Benign according to our data. Variant chr18-49843388-C-T is described in ClinVar as Benign. ClinVar VariationId is 327010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.75 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.28 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.4464G>A	p.Leu1488Leu	synonymous	Exon 34 of 40	NP_001073936.1	Q9ULV0-1
	SNHG22	NR_117096.1		n.192+2963C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5B	ENST00000285039.12	TSL:1 MANE Select	c.4464G>A	p.Leu1488Leu	synonymous	Exon 34 of 40	ENSP00000285039.6	Q9ULV0-1
	MYO5B	ENST00000592688.1	TSL:1	c.174G>A	p.Leu58Leu	synonymous	Exon 3 of 9	ENSP00000466368.1	Q9ULV0-3
	MYO5B	ENST00000697219.1		c.4197G>A	p.Leu1399Leu	synonymous	Exon 32 of 38	ENSP00000513188.1	A0A8V8TM52

Frequencies

GnomAD3 genomes AF: 0.0790 AC: 12019 AN: 152044 Hom.: 941 Cov.: 33

Gnomad AFR AF: 0.0528

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.0383

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0647

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0477

Gnomad OTH AF: 0.0876

GnomAD2 exomes AF: 0.122 AC: 30529 AN: 249252 AF XY: 0.111

Gnomad AFR exome AF: 0.0534

Gnomad AMR exome AF: 0.383

Gnomad ASJ exome AF: 0.0372

Gnomad EAS exome AF: 0.287

Gnomad FIN exome AF: 0.0661

Gnomad NFE exome AF: 0.0481

Gnomad OTH exome AF: 0.0949

GnomAD4 exome AF: 0.0724 AC: 105856 AN: 1461804 Hom.: 8354 Cov.: 32 AF XY: 0.0722 AC XY: 52529 AN XY: 727212

African (AFR) AF: 0.0542 AC: 1816 AN: 33480

American (AMR) AF: 0.364 AC: 16299 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0364 AC: 952 AN: 26136

East Asian (EAS) AF: 0.357 AC: 14158 AN: 39698

South Asian (SAS) AF: 0.115 AC: 9941 AN: 86252

European-Finnish (FIN) AF: 0.0647 AC: 3456 AN: 53402

Middle Eastern (MID) AF: 0.0820 AC: 473 AN: 5768

European-Non Finnish (NFE) AF: 0.0487 AC: 54121 AN: 1111962

Other (OTH) AF: 0.0768 AC: 4640 AN: 60390

GnomAD4 genome AF: 0.0792 AC: 12049 AN: 152162 Hom.: 950 Cov.: 33 AF XY: 0.0840 AC XY: 6250 AN XY: 74376

African (AFR) AF: 0.0528 AC: 2191 AN: 41530

American (AMR) AF: 0.229 AC: 3499 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0383 AC: 133 AN: 3472

East Asian (EAS) AF: 0.292 AC: 1505 AN: 5152

South Asian (SAS) AF: 0.122 AC: 588 AN: 4822

European-Finnish (FIN) AF: 0.0647 AC: 685 AN: 10590

Middle Eastern (MID) AF: 0.0582 AC: 17 AN: 292

European-Non Finnish (NFE) AF: 0.0477 AC: 3241 AN: 68002

Other (OTH) AF: 0.0882 AC: 186 AN: 2110

Alfa AF: 0.0651 Hom.: 1091

Bravo AF: 0.0945

Asia WGS AF: 0.187 AC: 648 AN: 3478

EpiCase AF: 0.0488

EpiControl AF: 0.0480

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.6
DANN	Benign	0.59
PhyloP100		0.75
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2276170; hg19: chr18-47369758; COSMIC: COSV53213009; COSMIC: COSV53213009;