chr11-71793380-C-T

Variant names:

• chr11-71793380-C-T
• rs1951779436
• ENST00000526393.5:n.270C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000526393.5(ENSG00000291186):​n.270C>T variant causes a splice region, non coding transcript exon change. The variant allele was found at a frequency of 0.00000137 in 1,458,742 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ENSG00000291186 ENST00000526393.5 splice_region, non_coding_transcript_exon
• Scores: Splicing: ADA: 0.003526
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.73
• Publications: 0 publications found

Genes affected

ENSG00000291186 (HGNC:):

FAM86C1P (HGNC:25561): (family with sequence similarity 86 member C1, pseudogene) Predicted to enable protein-L-histidine N-tele-methyltransferase activity. Predicted to be involved in peptidyl-histidine methylation, to form tele-methylhistidine. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2738064).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000526393.5. 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
	ENSG00000291186	ENST00000526393.5	TSL:1	n.270C>T		splice_region non_coding_transcript_exon	Exon 4 of 5
	ENSG00000291186	ENST00000346333.12	TSL:1	n.652-2637C>T		intron	N/A
	ENSG00000291186	ENST00000510443.6	TSL:1	n.391+1561C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458742 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725706

African (AFR) AF: 0.00 AC: 0 AN: 32950

American (AMR) AF: 0.00 AC: 0 AN: 44596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86074

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111648

Other (OTH) AF: 0.0000166 AC: 1 AN: 60154

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.096	T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.089
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.0	T
PhyloP100		3.7
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.97	D
Vest4		0.38
MutPred		0.49		Loss of disorder (P = 0.0362)
MVP		0.17
MPC		0.77
ClinPred		0.96	D
GERP RS		2.0
Varity_R		0.47
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0035
dbscSNV1_RF	Benign	0.17
SpliceAI score (max)		0.050		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: rs1951779436; hg19: chr11-71504426;