rs754090623

Variant names:

• chr14-94100744-G-A
• rs754090623
• NM_206949.3:c.34G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-94100744-G-A
• chr14-94100744-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_206949.3(IFI27L1):​c.34G>A​(p.Ala12Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: IFI27L1 NM_206949.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

Genes affected

IFI27L1 (HGNC:19754): (interferon alpha inducible protein 27 like 1) Involved in apoptotic process. Predicted to be integral component of membrane. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05266878).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFI27L1	NM_206949.3	c.34G>A	p.Ala12Thr	missense_variant	Exon 3 of 5	ENST00000555523.6	NP_996832.1
IFI27L1	NM_145249.3	c.34G>A	p.Ala12Thr	missense_variant	Exon 3 of 5		NP_660292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFI27L1	ENST00000555523.6	c.34G>A	p.Ala12Thr	missense_variant	Exon 3 of 5	2	NM_206949.3	ENSP00000451851.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461238 Hom.: 0 Cov.: 33 AF XY: 0.00000963 AC XY: 7 AN XY: 726970

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.62
DANN	Benign	0.81
DEOGEN2	Benign	0.010	T;T;.;.;.;.;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0022	N
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.053	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.83	N;N;.;.;.;.;.;.
PROVEAN	Benign	-0.070	N;N;N;N;N;N;N;N
REVEL	Benign	0.0050
Sift	Benign	0.42	T;T;T;T;T;.;.;T
Sift4G	Benign	0.37	T;T;T;T;T;T;T;T
Polyphen		0.027	B;B;.;.;.;.;.;.
Vest4		0.061
MutPred		0.34		Gain of sheet (P = 0.0043);Gain of sheet (P = 0.0043);.;.;.;Gain of sheet (P = 0.0043);Gain of sheet (P = 0.0043);Gain of sheet (P = 0.0043);
MVP		0.014
MPC		0.038
ClinPred		0.043	T
GERP RS		-5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.020
gMVP		0.082

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs754090623; hg19: chr14-94567090;