Variant 22-42409525-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_145912.8(NFAM1):c.474G>A(p.Pro158=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00566 in 1,537,692 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0054 ( 8 hom., cov: 33)

Exomes 𝑓: 0.0057 ( 31 hom. )

Consequence

NFAM1
NM_145912.8 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -8.63

Variant links:

Genes affected

NFAM1 (HGNC:29872): (NFAT activating protein with ITAM motif 1) The protein encoded by this gene is a type I membrane receptor that activates cytokine gene promoters such as the IL-13 and TNF-alpha promoters. The encoded protein contains an immunoreceptor tyrosine-based activation motif (ITAM) and is thought to regulate the signaling and development of B-cells. [provided by RefSeq, Jul 2008]

NFAM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 22-42409525-C-T is Benign according to our data. Variant chr22-42409525-C-T is described in ClinVar as [Benign]. Clinvar id is 769482.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-8.63 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00569 (7881/1385440) while in subpopulation MID AF= 0.0186 (102/5470). AF 95% confidence interval is 0.0157. There are 31 homozygotes in gnomad4_exome. There are 3929 alleles in male gnomad4_exome subpopulation. Median coverage is 28. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NFAM1	NM_145912.8 linkuse as main transcript	c.474G>A	p.Pro158=	synonymous_variant	3/6	ENST00000329021.10	NP_666017.1
NFAM1	NM_001371362.1 linkuse as main transcript	c.318G>A	p.Pro106=	synonymous_variant	5/8		NP_001358291.1
NFAM1	NM_001318323.3 linkuse as main transcript	c.451+1882G>A		intron_variant			NP_001305252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NFAM1	ENST00000329021.10 linkuse as main transcript	c.474G>A	p.Pro158=	synonymous_variant	3/6	1	NM_145912.8	ENSP00000333680	P1

Frequencies

GnomAD3 genomes

AF:

0.00544

AC:

828

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0258

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00600

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00714

AC:

1408

AN:

197296

Hom.:

AF XY:

0.00730

AC XY:

787

AN XY:

107754

show subpopulations

Gnomad AFR exome

AF:

0.00130

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.00413

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00337

Gnomad FIN exome

AF:

0.0257

Gnomad NFE exome

AF:

0.00711

Gnomad OTH exome

AF:

0.00772

GnomAD4 exome

AF:

0.00569

AC:

7881

AN:

1385440

Hom.:

Cov.:

AF XY:

0.00572

AC XY:

3929

AN XY:

687324

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00305

Gnomad4 ASJ exome

AF:

0.00542

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00330

Gnomad4 FIN exome

AF:

0.0225

Gnomad4 NFE exome

AF:

0.00538

Gnomad4 OTH exome

AF:

0.00557

GnomAD4 genome

AF:

0.00543

AC:

827

AN:

152252

Hom.:

Cov.:

AF XY:

0.00627

AC XY:

467

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000891

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0258

Gnomad4 NFE

AF:

0.00600

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00507

Hom.:

Bravo

AF:

0.00421

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

-0.89

CADD

Benign

0.10

DANN

Benign

0.54

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over