rs184908312

Variant names:

• chr11-17477320-C-T
• rs184908312
• ENST00000662030.1:n.137+589C>T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2 BP4_Strong BP6 BS1

The ENST00000662030.1(ENSG00000287898):​n.137+589C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00076 in 128,900 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency: Genomes: 𝑓 0.00076 (1 hom., cov: 32)
• Consequence: ENSG00000287898 ENST00000662030.1 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:1
• Conservation: PhyloP100: -0.906

Genes affected

ENSG00000287898 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-17477320-C-T is Benign according to our data. Variant chr11-17477320-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 434041.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=2}.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00076 (98/128900) while in subpopulation EAS AF= 0.0203 (89/4386). AF 95% confidence interval is 0.0169. There are 1 homozygotes in gnomad4. There are 63 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124902641	XR_007062609.1	n.81+589C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000287898	ENST00000662030.1	n.137+589C>T		intron_variant	Intron 1 of 1
ENSG00000287898	ENST00000666786.1	n.124+266C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.000761 AC: 98 AN: 128786 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000169

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0203

Gnomad SAS AF: 0.000800

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000533

Gnomad OTH AF: 0.000562

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

GnomAD4 genome AF: 0.000760 AC: 98 AN: 128900 Hom.: 1 Cov.: 32 AF XY: 0.00100 AC XY: 63 AN XY: 62854

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000169

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0203

Gnomad4 SAS AF: 0.000800

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000533

Gnomad4 OTH AF: 0.000555

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000922

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Maturity onset diabetes mellitus in young Uncertain:1

-

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

Mutations in ABCC8 gene are associated with both neonatal diabetes mellitus as well as MODY. Patients with this mutation may have a better response to sulfonylureas. However, no sufficient evidence is found to ascertain the role of this particular variant ( rs184908312) in MODY yet. -

Transitory neonatal diabetes mellitus Uncertain:1

-

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

Mutations in ABCC8 gene are associated with both neonatal diabetes mellitus as well as MODY. Patients with this mutation may have a better response to sulfonylureas. However, no sufficient evidence is found to ascertain the role of this particular variant ( rs184908312) in neonatal diabetes yet. -

not specified Benign:1

Oct 25, 2017

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.79
DANN	Benign	0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs184908312; hg19: chr11-17498867;