3-41897008-G-C

Variant names:

• chr3-41897008-G-C
• rs1717005
• NM_017886.4:c.1349-5C>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017886.4(ULK4):​c.1349-5C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.984 in 1,604,058 control chromosomes in the GnomAD database, including 779,138 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.93 (66384 hom., cov: 31)
  • Exomes 𝑓: 0.99 (712754 hom.)
• Consequence: ULK4 NM_017886.4 splice_region, intron
• Scores: Splicing: ADA: 0.0002944
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.97

Genes affected

ULK4 (HGNC:15784): (unc-51 like kinase 4) This gene encodes a member of the unc-51-like serine/threonine kinase (STK) family. Members of this protein family play a role in neuronal growth and endocytosis. The encoded protein is likely involved in neurite branching, neurite elongation and neuronal migration. Genome-wide association studies (GWAS) indicate an association of variations in this gene with blood pressure and hypertension. Sequence variations in this gene may also be be associated with psychiatric disorders, including schizophrenia and bipolar disorder. Pseudogenes associated with this gene have been identified and are located on chromosome 15. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 3-41897008-G-C is Benign according to our data. Variant chr3-41897008-G-C is described in ClinVar as [Benign]. Clinvar id is 403587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK4	NM_017886.4	c.1349-5C>G		splice_region_variant, intron_variant	Intron 14 of 36	ENST00000301831.9	NP_060356.2
ULK4	NM_001322500.2	c.1349-5C>G		splice_region_variant, intron_variant	Intron 14 of 35		NP_001309429.1
ULK4	NM_001322501.2	c.443-5C>G		splice_region_variant, intron_variant	Intron 13 of 35		NP_001309430.1
ULK4	NR_136342.2	n.1415-5C>G		splice_region_variant, intron_variant	Intron 13 of 34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK4	ENST00000301831.9	c.1349-5C>G		splice_region_variant, intron_variant	Intron 14 of 36	2	NM_017886.4	ENSP00000301831.4
ULK4	ENST00000420927.5	c.1349-5C>G		splice_region_variant, intron_variant	Intron 14 of 17	1		ENSP00000412187.1

Frequencies

GnomAD3 genomes AF: 0.928 AC: 141195 AN: 152112 Hom.: 66356 Cov.: 31

Gnomad AFR AF: 0.760

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.964

Gnomad ASJ AF: 0.979

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.944

GnomAD3 exomes AF: 0.979 AC: 237951 AN: 243012 Hom.: 116908 AF XY: 0.984 AC XY: 130554 AN XY: 132698

Gnomad AFR exome AF: 0.753

Gnomad AMR exome AF: 0.981

Gnomad ASJ exome AF: 0.982

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.999

Gnomad FIN exome AF: 0.999

Gnomad NFE exome AF: 0.996

Gnomad OTH exome AF: 0.983

GnomAD4 exome AF: 0.990 AC: 1437410 AN: 1451828 Hom.: 712754 Cov.: 29 AF XY: 0.991 AC XY: 715964 AN XY: 722486

Gnomad4 AFR exome AF: 0.740

Gnomad4 AMR exome AF: 0.980

Gnomad4 ASJ exome AF: 0.981

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.998

Gnomad4 FIN exome AF: 0.999

Gnomad4 NFE exome AF: 0.998

Gnomad4 OTH exome AF: 0.978

GnomAD4 genome AF: 0.928 AC: 141269 AN: 152230 Hom.: 66384 Cov.: 31 AF XY: 0.930 AC XY: 69221 AN XY: 74438

Gnomad4 AFR AF: 0.760

Gnomad4 AMR AF: 0.964

Gnomad4 ASJ AF: 0.979

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 0.999

Gnomad4 NFE AF: 0.997

Gnomad4 OTH AF: 0.945

Alfa AF: 0.977 Hom.: 23488

Bravo AF: 0.917

Asia WGS AF: 0.975 AC: 3391 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.54
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00029
dbscSNV1_RF	Benign	0.048
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

Publications

LitVar

Other links and lift over

dbSNP: rs1717005; hg19: chr3-41938500;