chr19-38307446-T-C

Variant names:

• chr19-38307446-T-C
• rs3178327
• NM_001039672.3:c.771A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001039672.3(YIF1B):​c.771A>G​(p.Val257Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,613,022 control chromosomes in the GnomAD database, including 75,740 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (6836 hom., cov: 30)
  • Exomes 𝑓: 0.30 (68904 hom.)
• Consequence: YIF1B NM_001039672.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710
• Publications: 24 publications found

Genes affected

YIF1B (HGNC:30511): (Yip1 interacting factor homolog B, membrane trafficking protein) Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport; protein targeting to membrane; and sperm axoneme assembly. Located in Golgi apparatus; endoplasmic reticulum; and endoplasmic reticulum-Golgi intermediate compartment. [provided by Alliance of Genome Resources, Apr 2022]

YIF1B Gene-Disease associations (from GenCC):

• Kaya-Barakat-Masson syndrome

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=-0.071 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039672.3. 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
	YIF1B	NM_001039672.3	MANE Select	c.771A>G	p.Val257Val	synonymous	Exon 7 of 8	NP_001034761.1
	YIF1B	NM_001039673.3		c.762A>G	p.Val254Val	synonymous	Exon 7 of 8	NP_001034762.1
	YIF1B	NM_001039671.3		c.726A>G	p.Val242Val	synonymous	Exon 7 of 8	NP_001034760.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YIF1B	ENST00000339413.11	TSL:1 MANE Select	c.771A>G	p.Val257Val	synonymous	Exon 7 of 8	ENSP00000343435.5
	YIF1B	ENST00000337679.12	TSL:1	c.762A>G	p.Val254Val	synonymous	Exon 7 of 9	ENSP00000337411.7
	YIF1B	ENST00000392124.7	TSL:1	c.678A>G	p.Val226Val	synonymous	Exon 6 of 7	ENSP00000375971.2

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43153 AN: 151474 Hom.: 6825 Cov.: 30

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.268

GnomAD2 exomes AF: 0.344 AC: 85870 AN: 249862 AF XY: 0.341

Gnomad AFR exome AF: 0.181

Gnomad AMR exome AF: 0.469

Gnomad ASJ exome AF: 0.292

Gnomad EAS exome AF: 0.547

Gnomad FIN exome AF: 0.413

Gnomad NFE exome AF: 0.273

Gnomad OTH exome AF: 0.326

GnomAD4 exome AF: 0.298 AC: 435313 AN: 1461428 Hom.: 68904 Cov.: 37 AF XY: 0.300 AC XY: 218378 AN XY: 727000

African (AFR) AF: 0.183 AC: 6124 AN: 33480

American (AMR) AF: 0.469 AC: 20931 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 7641 AN: 26134

East Asian (EAS) AF: 0.547 AC: 21725 AN: 39692

South Asian (SAS) AF: 0.391 AC: 33753 AN: 86246

European-Finnish (FIN) AF: 0.405 AC: 21552 AN: 53196

Middle Eastern (MID) AF: 0.304 AC: 1755 AN: 5768

European-Non Finnish (NFE) AF: 0.273 AC: 303461 AN: 1111868

Other (OTH) AF: 0.304 AC: 18371 AN: 60374

GnomAD4 genome AF: 0.285 AC: 43215 AN: 151594 Hom.: 6836 Cov.: 30 AF XY: 0.298 AC XY: 22089 AN XY: 74058

African (AFR) AF: 0.185 AC: 7633 AN: 41364

American (AMR) AF: 0.391 AC: 5940 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1023 AN: 3472

East Asian (EAS) AF: 0.561 AC: 2870 AN: 5120

South Asian (SAS) AF: 0.397 AC: 1911 AN: 4808

European-Finnish (FIN) AF: 0.431 AC: 4516 AN: 10482

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.273 AC: 18504 AN: 67856

Other (OTH) AF: 0.270 AC: 568 AN: 2100

Alfa AF: 0.279 Hom.: 10746

Bravo AF: 0.280

Asia WGS AF: 0.445 AC: 1543 AN: 3478

EpiCase AF: 0.272

EpiControl AF: 0.270

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.5
DANN	Benign	0.66
PhyloP100		-0.071
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.9
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: rs3178327; hg19: chr19-38798086; COSMIC: COSV56650288; COSMIC: COSV56650288;