11-71796083-G-A

Variant names:

• chr11-71796083-G-A
• rs145777517
• ENST00000346333.12:n.718G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000346333.12(ENSG00000291186):​n.718G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,595,778 control chromosomes in the GnomAD database, including 3 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 0.0037 (0 hom., cov: 35)
  • Exomes 𝑓: 0.0014 (3 hom.)
• Consequence: ENSG00000291186 ENST00000346333.12 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.11
• Publications: 7 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]

ALG1L9P (HGNC:44378): (ALG1 like 9, pseudogene)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0043332875).
• BS2: High Homozygotes in GnomAdExome4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000346333.12. 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
	ALG1L9P	NR_073388.1		n.739C>T		non_coding_transcript_exon	Exon 4 of 4
	ALG1L9P	NR_073386.1		n.697-829C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000291186	ENST00000346333.12	TSL:1	n.718G>A		non_coding_transcript_exon	Exon 3 of 4
	ENSG00000291186	ENST00000510443.6	TSL:1	n.458G>A		non_coding_transcript_exon	Exon 4 of 5
	ENSG00000291186	ENST00000526393.5	TSL:1	n.438G>A		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes AF: 0.00368 AC: 540 AN: 146768 Hom.: 0 Cov.: 35

Gnomad AFR AF: 0.00886

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000667

Gnomad ASJ AF: 0.000874

Gnomad EAS AF: 0.00319

Gnomad SAS AF: 0.00534

Gnomad FIN AF: 0.000767

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00199

Gnomad OTH AF: 0.00299

GnomAD2 exomes AF: 0.00171 AC: 424 AN: 247802 AF XY: 0.00142

Gnomad AFR exome AF: 0.0105

Gnomad AMR exome AF: 0.000437

Gnomad ASJ exome AF: 0.000299

Gnomad EAS exome AF: 0.00124

Gnomad FIN exome AF: 0.00102

Gnomad NFE exome AF: 0.00101

Gnomad OTH exome AF: 0.000821

GnomAD4 exome AF: 0.00138 AC: 2003 AN: 1448902 Hom.: 3 Cov.: 50 AF XY: 0.00145 AC XY: 1046 AN XY: 720970

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00605 AC: 186 AN: 30764

American (AMR) AF: 0.000473 AC: 21 AN: 44382

Ashkenazi Jewish (ASJ) AF: 0.000154 AC: 4 AN: 25994

East Asian (EAS) AF: 0.00242 AC: 94 AN: 38784

South Asian (SAS) AF: 0.00336 AC: 287 AN: 85490

European-Finnish (FIN) AF: 0.000828 AC: 44 AN: 53166

Middle Eastern (MID) AF: 0.00381 AC: 20 AN: 5252

European-Non Finnish (NFE) AF: 0.00113 AC: 1247 AN: 1105442

Other (OTH) AF: 0.00168 AC: 100 AN: 59628

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00369 AC: 542 AN: 146876 Hom.: 0 Cov.: 35 AF XY: 0.00338 AC XY: 243 AN XY: 71812

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00888 AC: 341 AN: 38384

American (AMR) AF: 0.000666 AC: 10 AN: 15004

Ashkenazi Jewish (ASJ) AF: 0.000874 AC: 3 AN: 3432

East Asian (EAS) AF: 0.00320 AC: 16 AN: 4996

South Asian (SAS) AF: 0.00535 AC: 25 AN: 4676

European-Finnish (FIN) AF: 0.000767 AC: 8 AN: 10430

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.00199 AC: 133 AN: 66730

Other (OTH) AF: 0.00296 AC: 6 AN: 2030

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00336 Hom.: 0

ExAC AF: 0.00843 AC: 1023

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	0.028
DANN	Benign	0.93
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.0043	T
MetaSVM	Benign	-1.1	T
PhyloP100		-3.1
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.084	B
Vest4		0.20
MutPred		0.23		Gain of MoRF binding (P = 0.0217)
MVP		0.061
MPC		0.52
ClinPred		0.056	T
GERP RS		-1.8
Varity_R		0.11
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs145777517; hg19: chr11-71507129; COSMIC: COSV60641156; COSMIC: COSV60641156;