9-21440549-C-T

Position:

• chr9-21440549-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_024013.3(IFNA1):​c.42C>T​(p.Leu14=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,613,332 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0064 (6 hom., cov: 26)
  • Exomes 𝑓: 0.0013 (19 hom.)
• Consequence: IFNA1 NM_024013.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.17

Genes affected

IFNA1 (HGNC:5417): (interferon alpha 1) This gene is a member of the alpha interferon gene cluster on chromosome 9. The encoded cytokine is a member of the type I interferon family that is produced in response to viral infection as a key part of the innate immune response with potent antiviral, antiproliferative and immunomodulatory properties. This cytokine, like other type I interferons, binds a plasma membrane receptor made of IFNAR1 and IFNAR2 that is ubiquitously expressed, and thus is able to act on virtually all body cells. This cytokine is upregulated in preeclamptic placentas and is thought to be a mediator of preeclampsia. [provided by RefSeq, Aug 2020]

MIR31HG (HGNC:37187): (MIR31 host gene) This gene produces a long non-coding RNA that acts as a host gene for miR-31. This transcript may be involved in cellular pluripotency and regulate the differentiation of myoblasts and other tissues. This RNA was found to interact with Polycomb repressive proteins to repression transcription of genes involves in cell senescence. [provided by RefSeq, Dec 2017]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 9-21440549-C-T is Benign according to our data. Variant chr9-21440549-C-T is described in ClinVar as [Benign]. Clinvar id is 775272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.17 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00636 (967/152148) while in subpopulation AFR AF= 0.0172 (715/41490). AF 95% confidence interval is 0.0162. There are 6 homozygotes in gnomad4. There are 475 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFNA1	NM_024013.3	c.42C>T	p.Leu14=	synonymous_variant	1/1	ENST00000276927.3	NP_076918.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFNA1	ENST00000276927.3	c.42C>T	p.Leu14=	synonymous_variant	1/1		NM_024013.3	ENSP00000276927	P1
MIR31HG	ENST00000698343.1	n.103-19857G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00635 AC: 965 AN: 152030 Hom.: 6 Cov.: 26

Gnomad AFR AF: 0.0173

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00793

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000838

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00240 AC: 602 AN: 250976 Hom.: 6 AF XY: 0.00201 AC XY: 272 AN XY: 135614

Gnomad AFR exome AF: 0.0170

Gnomad AMR exome AF: 0.00269

Gnomad ASJ exome AF: 0.00851

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000294

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000987

Gnomad OTH exome AF: 0.00427

GnomAD4 exome AF: 0.00131 AC: 1919 AN: 1461184 Hom.: 19 Cov.: 32 AF XY: 0.00130 AC XY: 942 AN XY: 726858

Gnomad4 AFR exome AF: 0.0184

Gnomad4 AMR exome AF: 0.00304

Gnomad4 ASJ exome AF: 0.0111

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000406

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000497

Gnomad4 OTH exome AF: 0.00345

GnomAD4 genome AF: 0.00636 AC: 967 AN: 152148 Hom.: 6 Cov.: 26 AF XY: 0.00638 AC XY: 475 AN XY: 74400

Gnomad4 AFR AF: 0.0172

Gnomad4 AMR AF: 0.00792

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000624

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000838

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00357 Hom.: 3

Bravo AF: 0.00754

EpiCase AF: 0.00234

EpiControl AF: 0.00213

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
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.0
DANN	Benign	0.71

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: rs34278127; hg19: chr9-21440548;