NM_145912.8:c.121+9088T>C

Variant names:

• chr22-42423149-A-G
• rs9611791
• NM_145912.8:c.121+9088T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145912.8(NFAM1):​c.121+9088T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 145,730 control chromosomes in the GnomAD database, including 33,397 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 0.66 (33397 hom., cov: 23)
• Consequence: NFAM1 NM_145912.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.345
• Publications: 0 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145912.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFAM1	NM_145912.8	MANE Select	c.121+9088T>C		intron	N/A	NP_666017.1
	NFAM1	NM_001371362.1		c.-35-11413T>C		intron	N/A	NP_001358291.1
	NFAM1	NM_001318323.3		c.121+9088T>C		intron	N/A	NP_001305252.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFAM1	ENST00000329021.10	TSL:1 MANE Select	c.121+9088T>C		intron	N/A	ENSP00000333680.5
	NFAM1	ENST00000355469.4	TSL:3	n.126+9088T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.665 AC: 96786 AN: 145646 Hom.: 33352 Cov.: 23

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.644

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.665 AC: 96877 AN: 145730 Hom.: 33397 Cov.: 23 AF XY: 0.659 AC XY: 46484 AN XY: 70538

African (AFR) AF: 0.844 AC: 32584 AN: 38606

American (AMR) AF: 0.700 AC: 9991 AN: 14270

Ashkenazi Jewish (ASJ) AF: 0.639 AC: 2195 AN: 3434

East Asian (EAS) AF: 0.418 AC: 2100 AN: 5022

South Asian (SAS) AF: 0.701 AC: 3264 AN: 4658

European-Finnish (FIN) AF: 0.505 AC: 4693 AN: 9290

Middle Eastern (MID) AF: 0.643 AC: 184 AN: 286

European-Non Finnish (NFE) AF: 0.594 AC: 39977 AN: 67254

Other (OTH) AF: 0.647 AC: 1309 AN: 2022

Alfa AF: 0.617 Hom.: 9474

Bravo AF: 0.692

Asia WGS AF: 0.624 AC: 2173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.82
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9611791; hg19: chr22-42819155;