10-89418391-C-T

Position:

• chr10-89418391-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000371795.5(IFIT5):​c.1192C>T​(p.His398Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 1,614,160 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (25 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (16 hom.)
• Consequence: IFIT5 ENST00000371795.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.943

Genes affected

IFIT5 (HGNC:13328): (interferon induced protein with tetratricopeptide repeats 5) Enables nucleic acid binding activity. Involved in defense response to virus; negative regulation of viral genome replication; and positive regulation of I-kappaB kinase/NF-kappaB signaling. Located in actin cytoskeleton; apical part of cell; and ruffle membrane. Colocalizes with IkappaB kinase complex. [provided by Alliance of Genome Resources, Apr 2022]

LOC107984251 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0032732189).
• BP6: Variant 10-89418391-C-T is Benign according to our data. Variant chr10-89418391-C-T is described in ClinVar as [Benign]. Clinvar id is 781214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.01 (1527/152294) while in subpopulation AFR AF= 0.0347 (1444/41560). AF 95% confidence interval is 0.0333. There are 25 homozygotes in gnomad4. There are 710 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFIT5	NM_012420.3	c.1192C>T	p.His398Tyr	missense_variant	2/2	ENST00000371795.5	NP_036552.1
LOC107984251	XR_001747541.2	n.74-2586G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFIT5	ENST00000371795.5	c.1192C>T	p.His398Tyr	missense_variant	2/2	1	NM_012420.3	ENSP00000360860	P1

Frequencies

GnomAD3 genomes AF: 0.0100 AC: 1524 AN: 152176 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.0348

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00353

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00717

GnomAD3 exomes AF: 0.00264 AC: 664 AN: 251432 Hom.: 11 AF XY: 0.00194 AC XY: 264 AN XY: 135904

Gnomad AFR exome AF: 0.0341

Gnomad AMR exome AF: 0.00202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000237

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00109 AC: 1592 AN: 1461866 Hom.: 16 Cov.: 34 AF XY: 0.000961 AC XY: 699 AN XY: 727230

Gnomad4 AFR exome AF: 0.0350

Gnomad4 AMR exome AF: 0.00224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000114

Gnomad4 OTH exome AF: 0.00277

GnomAD4 genome AF: 0.0100 AC: 1527 AN: 152294 Hom.: 25 Cov.: 32 AF XY: 0.00953 AC XY: 710 AN XY: 74482

Gnomad4 AFR AF: 0.0347

Gnomad4 AMR AF: 0.00353

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00183 Hom.: 10

Bravo AF: 0.0115

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0343 AC: 151

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00313 AC: 380

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.83
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.14	T
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	0.99	N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.063
Sift	Benign	1.0	T
Sift4G	Benign	0.41	T
Polyphen		0.0060	B
Vest4		0.17
MVP		0.60
MPC		0.19
ClinPred		0.0065	T
GERP RS		4.3
Varity_R		0.20
gMVP		0.097

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

Publications

LitVar

Other links and lift over

dbSNP: rs114336814; hg19: chr10-91178148;