Genetic Variant NM_145912.8:c.*2149A>G (chr22-42383012-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_145912.8(NFAM1):c.*2149A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,676 control chromosomes in the GnomAD database, including 8,174 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 0.32 ( 8115 hom., cov: 32)

Exomes 𝑓: 0.34 ( 59 hom. )

Consequence

NFAM1
NM_145912.8 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.439

Publications

4 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
NFAM1	NM_145912.8 link	c.*2149A>G	3_prime_UTR_variant	Exon 6 of 6	ENST00000329021.10	NP_666017.1	Q8NET5
NFAM1	NM_001371362.1 link	c.*2149A>G	3_prime_UTR_variant	Exon 8 of 8		NP_001358291.1
NFAM1	NM_001318323.3 link	c.*2252A>G	3_prime_UTR_variant	Exon 5 of 5		NP_001305252.1	Q8NET5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NFAM1	ENST00000329021.10 link	c.*2149A>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_145912.8	ENSP00000333680.5		Q8NET5

Frequencies

GnomAD3 genomes

AF:

0.318

AC:

48168

AN:

151620

Hom.:

8103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.211

Gnomad AMI

AF:

0.545

Gnomad AMR

AF:

0.420

Gnomad ASJ

AF:

0.319

Gnomad EAS

AF:

0.244

Gnomad SAS

AF:

0.361

Gnomad FIN

AF:

0.339

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.355

Gnomad OTH

AF:

0.324

GnomAD4 exome

AF:

0.339

AC:

318

AN:

938

Hom.:

Cov.:

AF XY:

0.351

AC XY:

252

AN XY:

718

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.208

AC:

AN:

South Asian (SAS)

AF:

0.344

AC:

AN:

European-Finnish (FIN)

AF:

0.327

AC:

AN:

Middle Eastern (MID)

AF:

0.750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.332

AC:

241

AN:

726

Other (OTH)

AF:

0.423

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.318

AC:

48201

AN:

151738

Hom.:

8115

Cov.:

AF XY:

0.319

AC XY:

23661

AN XY:

74154

show subpopulations

African (AFR)

AF:

0.211

AC:

8723

AN:

41348

American (AMR)

AF:

0.420

AC:

6406

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.319

AC:

1106

AN:

3464

East Asian (EAS)

AF:

0.244

AC:

1255

AN:

5138

South Asian (SAS)

AF:

0.362

AC:

1736

AN:

4794

European-Finnish (FIN)

AF:

0.339

AC:

3573

AN:

10544

Middle Eastern (MID)

AF:

0.333

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.355

AC:

24119

AN:

67882

Other (OTH)

AF:

0.328

AC:

692

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1695

3390

5085

6780

8475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

474

948

1422

1896

2370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.323

Hom.:

1781

Bravo

AF:

0.324

Asia WGS

AF:

0.339

AC:

1181

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.4

(source)

DANN

Benign

0.44

PhyloP100

0.44

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over