11-1219991-G-T

Variant names:

• chr11-1219991-G-T
• rs35705950
• ENST00000654177.1:n.661G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000654177.1(ENSG00000286275):​n.661G>T variant causes a splice region, non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0793 in 152,220 control chromosomes in the GnomAD database, including 596 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign,risk factor (★★).

• Frequency: Genomes: 𝑓 0.079 (596 hom., cov: 33)
• Consequence: ENSG00000286275 ENST00000654177.1 splice_region, non_coding_transcript_exon
• Clinical Significance: Benign; risk factor criteria provided, multiple submitters, no conflicts U:1 B:1 O:3
• Conservation: PhyloP100: 0.183
• Publications: 514 publications found

Genes affected

ENSG00000286275 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 11-1219991-G-T is Benign according to our data. Variant chr11-1219991-G-T is described in ClinVar as Benign|risk_factor. ClinVar VariationId is 30126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000654177.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000286275	ENST00000654177.1		n.661G>T		splice_region non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0794 AC: 12074 AN: 152102 Hom.: 595 Cov.: 33

Gnomad AFR AF: 0.0206

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.0851

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.00694

Gnomad SAS AF: 0.0838

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0861

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

GnomAD4 genome AF: 0.0793 AC: 12074 AN: 152220 Hom.: 596 Cov.: 33 AF XY: 0.0803 AC XY: 5978 AN XY: 74428

African (AFR) AF: 0.0206 AC: 854 AN: 41546

American (AMR) AF: 0.0850 AC: 1301 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 407 AN: 3470

East Asian (EAS) AF: 0.00695 AC: 36 AN: 5178

South Asian (SAS) AF: 0.0849 AC: 410 AN: 4830

European-Finnish (FIN) AF: 0.115 AC: 1217 AN: 10590

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7499 AN: 67988

Other (OTH) AF: 0.0843 AC: 178 AN: 2112

Alfa AF: 0.0545 Hom.: 108

Bravo AF: 0.0747

ClinVar

ClinVar submissions

Significance: Benign; risk factor

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	1	-	Susceptibility to coronavirus disease (COVID-19) severity and mortality due to low plasma levels of MUC5B (1)
-	-	-	Antisynthetase syndrome (1)
-	-	-	Interstitial lung disease 2 (1)
-	-	-	Pulmonary fibrosis, idiopathic, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.3
DANN	Benign	0.69
PhyloP100		0.18

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs35705950;

hg19: chr11-1241221;