rs11954744

Variant names:

• chr5-144161839-T-A
• rs11954744
• NM_030799.9:c.611+379A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030799.9(YIPF5):​c.611+379A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,222 control chromosomes in the GnomAD database, including 1,937 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 0.15 (1937 hom., cov: 31)
• Consequence: YIPF5 NM_030799.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• Publications: 2 publications found

Genes affected

YIPF5 (HGNC:24877): (Yip1 domain family member 5) Predicted to be involved in endoplasmic reticulum to Golgi vesicle-mediated transport; regulation of ER to Golgi vesicle-mediated transport; and vesicle fusion with Golgi apparatus. Located in Golgi apparatus; endoplasmic reticulum; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

YIPF5 Gene-Disease associations (from GenCC):

• microcephaly, epilepsy, and diabetes syndrome 2

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• primary microcephaly-epilepsy-permanent neonatal diabetes syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YIPF5	NM_030799.9	c.611+379A>T		intron_variant	Intron 5 of 5	ENST00000274496.10	NP_110426.4
YIPF5	NM_001024947.4	c.611+379A>T		intron_variant	Intron 5 of 5		NP_001020118.1
YIPF5	NM_001271732.2	c.449+379A>T		intron_variant	Intron 4 of 4		NP_001258661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YIPF5	ENST00000274496.10	c.611+379A>T		intron_variant	Intron 5 of 5	1	NM_030799.9	ENSP00000274496.5
YIPF5	ENST00000448443.6	c.611+379A>T		intron_variant	Intron 5 of 5	1		ENSP00000397704.2
YIPF5	ENST00000513112.5	c.449+379A>T		intron_variant	Intron 4 of 4	1		ENSP00000425422.1
YIPF5	ENST00000519064.5	c.449+379A>T		intron_variant	Intron 4 of 4	2		ENSP00000429777.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23240 AN: 152104 Hom.: 1934 Cov.: 31

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.0196

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.174

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.153 AC: 23248 AN: 152222 Hom.: 1937 Cov.: 31 AF XY: 0.152 AC XY: 11300 AN XY: 74406

African (AFR) AF: 0.128 AC: 5310 AN: 41542

American (AMR) AF: 0.245 AC: 3749 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 700 AN: 3472

East Asian (EAS) AF: 0.0195 AC: 101 AN: 5184

South Asian (SAS) AF: 0.142 AC: 684 AN: 4828

European-Finnish (FIN) AF: 0.100 AC: 1062 AN: 10596

Middle Eastern (MID) AF: 0.209 AC: 61 AN: 292

European-Non Finnish (NFE) AF: 0.164 AC: 11131 AN: 68002

Other (OTH) AF: 0.172 AC: 363 AN: 2110

Alfa AF: 0.165 Hom.: 273

Bravo AF: 0.164

Asia WGS AF: 0.0840 AC: 293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.69
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11954744; hg19: chr5-143541403;