chr2-127566696-C-G

Variant names:

• chr2-127566696-C-G
• rs145802059
• NM_001393586.1:c.339C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001393586.1(MYO7B):​c.339C>G​(p.Leu113Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,609,518 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (29 hom.)
• Consequence: MYO7B NM_001393586.1 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.277
• Publications: 0 publications found

Genes affected

MYO7B (HGNC:7607): (myosin VIIB) The protein encoded by this gene is found in brush border microvilli of epithelial cells in the intestines and kidneys. The encoded protein is involved in linking protocadherins to the actin cytoskeleton and is essential for proper microvilli function. This protein aids in the accumulation of intermicrovillar adhesion components such as harmonin and ANKS4B, and this accumulation is necessary for normal brush border action. [provided by RefSeq, Jan 2017]

LOC105373609 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 2-127566696-C-G is Benign according to our data. Variant chr2-127566696-C-G is described in ClinVar as Benign. ClinVar VariationId is 3038634.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.277 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 29 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393586.1. 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
	MYO7B	NM_001393586.1	MANE Select	c.339C>G	p.Leu113Leu	synonymous	Exon 5 of 48	NP_001380515.1	A0A8C8KL71
	MYO7B	NM_001080527.2		c.339C>G	p.Leu113Leu	synonymous	Exon 5 of 47	NP_001073996.1	Q6PIF6-1
	LOC105373609	NR_132317.1		n.83-1909G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO7B	ENST00000409816.8	TSL:1 MANE Select	c.339C>G	p.Leu113Leu	synonymous	Exon 5 of 48	ENSP00000386461.3	A0A8C8KL71
	MYO7B	ENST00000897059.1		c.339C>G	p.Leu113Leu	synonymous	Exon 5 of 48	ENSP00000567118.1
	MYO7B	ENST00000428314.5	TSL:5	c.339C>G	p.Leu113Leu	synonymous	Exon 5 of 47	ENSP00000415090.1	Q6PIF6-1

Frequencies

GnomAD3 genomes AF: 0.00195 AC: 297 AN: 152258 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0159

Gnomad FIN AF: 0.000564

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00181

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00339 AC: 818 AN: 241146 AF XY: 0.00415

Gnomad AFR exome AF: 0.000404

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00222

Gnomad EAS exome AF: 0.0000571

Gnomad FIN exome AF: 0.000708

Gnomad NFE exome AF: 0.00212

Gnomad OTH exome AF: 0.00255

GnomAD4 exome AF: 0.00242 AC: 3525 AN: 1457142 Hom.: 29 Cov.: 31 AF XY: 0.00288 AC XY: 2084 AN XY: 724700

African (AFR) AF: 0.000269 AC: 9 AN: 33428

American (AMR) AF: 0.00145 AC: 64 AN: 44116

Ashkenazi Jewish (ASJ) AF: 0.00227 AC: 59 AN: 26044

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39534

South Asian (SAS) AF: 0.0156 AC: 1338 AN: 85658

European-Finnish (FIN) AF: 0.000424 AC: 22 AN: 51830

Middle Eastern (MID) AF: 0.00729 AC: 42 AN: 5758

European-Non Finnish (NFE) AF: 0.00166 AC: 1843 AN: 1110532

Other (OTH) AF: 0.00244 AC: 147 AN: 60242

GnomAD4 genome AF: 0.00193 AC: 294 AN: 152376 Hom.: 1 Cov.: 33 AF XY: 0.00224 AC XY: 167 AN XY: 74514

African (AFR) AF: 0.000240 AC: 10 AN: 41596

American (AMR) AF: 0.00431 AC: 66 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.0153 AC: 74 AN: 4830

European-Finnish (FIN) AF: 0.000564 AC: 6 AN: 10630

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00181 AC: 123 AN: 68030

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00138 Hom.: 0

Bravo AF: 0.00181

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MYO7B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	3.7
DANN	Benign	0.76
PhyloP100		0.28
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs145802059; hg19: chr2-128324271;