rs3826579

Variant names:

• chr18-49872179-G-A
• rs3826579
• NM_001080467.3:c.3591C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-49872179-G-A
• chr18-49872179-G-C
• chr18-49872179-G-T

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.3591C>T​(p.Tyr1197Tyr) variant causes a synonymous change. The variant allele was found at a frequency of 0.22 in 1,613,140 control chromosomes in the GnomAD database, including 41,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4531 hom., cov: 32)
  • Exomes 𝑓: 0.22 (36902 hom.)
• Consequence: MYO5B NM_001080467.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 3.95
• Publications: 18 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]

MYO5B Gene-Disease associations (from GenCC):

• microvillus inclusion disease

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• cholestasis, progressive familial intrahepatic, 10

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• progressive familial intrahepatic cholestasis type 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 18-49872179-G-A is Benign according to our data. Variant chr18-49872179-G-A is described in ClinVar as Benign. ClinVar VariationId is 327025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.405 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.3591C>T	p.Tyr1197Tyr	synonymous	Exon 27 of 40	NP_001073936.1	Q9ULV0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5B	ENST00000285039.12	TSL:1 MANE Select	c.3591C>T	p.Tyr1197Tyr	synonymous	Exon 27 of 40	ENSP00000285039.6	Q9ULV0-1
	MYO5B	ENST00000697219.1		c.3387C>T	p.Tyr1129Tyr	synonymous	Exon 25 of 38	ENSP00000513188.1	A0A8V8TM52
	MYO5B	ENST00000908785.1		c.3591C>T	p.Tyr1197Tyr	synonymous	Exon 27 of 28	ENSP00000578844.1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36500 AN: 151886 Hom.: 4523 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.225

GnomAD2 exomes AF: 0.255 AC: 63750 AN: 249532 AF XY: 0.256

Gnomad AFR exome AF: 0.269

Gnomad AMR exome AF: 0.264

Gnomad ASJ exome AF: 0.226

Gnomad EAS exome AF: 0.434

Gnomad FIN exome AF: 0.258

Gnomad NFE exome AF: 0.201

Gnomad OTH exome AF: 0.247

GnomAD4 exome AF: 0.218 AC: 318281 AN: 1461136 Hom.: 36902 Cov.: 33 AF XY: 0.221 AC XY: 160636 AN XY: 726914

African (AFR) AF: 0.268 AC: 8955 AN: 33462

American (AMR) AF: 0.262 AC: 11716 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 5858 AN: 26130

East Asian (EAS) AF: 0.384 AC: 15237 AN: 39698

South Asian (SAS) AF: 0.339 AC: 29224 AN: 86234

European-Finnish (FIN) AF: 0.258 AC: 13754 AN: 53406

Middle Eastern (MID) AF: 0.236 AC: 1354 AN: 5744

European-Non Finnish (NFE) AF: 0.196 AC: 218243 AN: 1111382

Other (OTH) AF: 0.231 AC: 13940 AN: 60360

GnomAD4 genome AF: 0.240 AC: 36546 AN: 152004 Hom.: 4531 Cov.: 32 AF XY: 0.246 AC XY: 18267 AN XY: 74290

African (AFR) AF: 0.273 AC: 11301 AN: 41444

American (AMR) AF: 0.247 AC: 3768 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 745 AN: 3466

East Asian (EAS) AF: 0.419 AC: 2160 AN: 5152

South Asian (SAS) AF: 0.341 AC: 1640 AN: 4806

European-Finnish (FIN) AF: 0.258 AC: 2730 AN: 10564

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13482 AN: 67982

Other (OTH) AF: 0.228 AC: 479 AN: 2104

Alfa AF: 0.216 Hom.: 10361

Bravo AF: 0.240

Asia WGS AF: 0.362 AC: 1258 AN: 3478

EpiCase AF: 0.201

EpiControl AF: 0.201

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Congenital microvillous atrophy (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	5.8
DANN	Benign	0.86
PhyloP100		3.9
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: rs3826579; hg19: chr18-47398549; COSMIC: COSV53214007; COSMIC: COSV53214007;