rs9611791

Positions:

• chr22-42423149-A-G
• chr22-42423149-A-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NFAM1	NM_145912.8	c.121+9088T>C		intron_variant		ENST00000329021.10
NFAM1	NM_001318323.3	c.121+9088T>C		intron_variant
NFAM1	NM_001371362.1	c.-35-11413T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NFAM1	ENST00000329021.10	c.121+9088T>C		intron_variant		1	NM_145912.8	P1
NFAM1	ENST00000355469.4	n.126+9088T>C		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.844

Gnomad4 AMR AF: 0.700

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.701

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.594

Gnomad4 OTH AF: 0.647

Alfa AF: 0.610 Hom.: 4543

Bravo AF: 0.692

Asia WGS AF: 0.624 AC: 2173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.82

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: rs9611791; hg19: chr22-42819155;