chr18-49836639-C-T

Variant names:

• chr18-49836639-C-T
• rs621101
• NM_001080467.3:c.5313+72G>A

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.5313+72G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 1,565,058 control chromosomes in the GnomAD database, including 166,382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15078 hom., cov: 32)
  • Exomes 𝑓: 0.45 (151304 hom.)
• Consequence: MYO5B NM_001080467.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.362
• Publications: 8 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]

ENSG00000266997 (HGNC:):

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=-0.84).
• BP6: Variant 18-49836639-C-T is Benign according to our data. Variant chr18-49836639-C-T is described in ClinVar as Benign. ClinVar VariationId is 1278709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.485 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.5313+72G>A		intron	N/A	NP_001073936.1
	SNHG22	NR_117096.1		n.41-2637C>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.5313+72G>A		intron	N/A	ENSP00000285039.6
	MYO5B	ENST00000592688.1	TSL:1	c.1023+72G>A		intron	N/A	ENSP00000466368.1
	ENSG00000266997	ENST00000590532.2	TSL:5	n.282+72G>A		intron	N/A	ENSP00000467396.2

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66387 AN: 151852 Hom.: 15074 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.478

GnomAD4 exome AF: 0.454 AC: 641929 AN: 1413088 Hom.: 151304 AF XY: 0.452 AC XY: 319059 AN XY: 705952

African (AFR) AF: 0.432 AC: 14022 AN: 32476

American (AMR) AF: 0.271 AC: 12072 AN: 44532

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 14660 AN: 25752

East Asian (EAS) AF: 0.117 AC: 4597 AN: 39422

South Asian (SAS) AF: 0.311 AC: 26374 AN: 84814

European-Finnish (FIN) AF: 0.388 AC: 20625 AN: 53112

Middle Eastern (MID) AF: 0.485 AC: 2745 AN: 5662

European-Non Finnish (NFE) AF: 0.487 AC: 520817 AN: 1068556

Other (OTH) AF: 0.443 AC: 26017 AN: 58762

GnomAD4 genome AF: 0.437 AC: 66417 AN: 151970 Hom.: 15078 Cov.: 32 AF XY: 0.430 AC XY: 31945 AN XY: 74282

African (AFR) AF: 0.423 AC: 17537 AN: 41410

American (AMR) AF: 0.371 AC: 5675 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1986 AN: 3464

East Asian (EAS) AF: 0.109 AC: 566 AN: 5184

South Asian (SAS) AF: 0.296 AC: 1422 AN: 4812

European-Finnish (FIN) AF: 0.395 AC: 4169 AN: 10544

Middle Eastern (MID) AF: 0.548 AC: 160 AN: 292

European-Non Finnish (NFE) AF: 0.490 AC: 33297 AN: 67966

Other (OTH) AF: 0.474 AC: 1001 AN: 2110

Alfa AF: 0.477 Hom.: 20906

Bravo AF: 0.435

Asia WGS AF: 0.247 AC: 860 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	-0.84
CADD	Benign	1.9
DANN	Benign	0.68
PhyloP100		-0.36
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: rs621101; hg19: chr18-47363009; COSMIC: COSV53235084; COSMIC: COSV53235084;