chr1-7938903-T-G

Variant names:

• chr1-7938903-T-G
• rs226476
• NM_001561.6:c.101-75A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001561.6(TNFRSF9):​c.101-75A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.966 in 1,013,220 control chromosomes in the GnomAD database, including 472,731 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.97 (72084 hom., cov: 33)
  • Exomes 𝑓: 0.96 (400647 hom.)
• Consequence: TNFRSF9 NM_001561.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.290
• Publications: 13 publications found

Genes affected

TNFRSF9 (HGNC:11924): (TNF receptor superfamily member 9) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor contributes to the clonal expansion, survival, and development of T cells. It can also induce proliferation in peripheral monocytes, enhance T cell apoptosis induced by TCR/CD3 triggered activation, and regulate CD28 co-stimulation to promote Th1 cell responses. The expression of this receptor is induced by lymphocyte activation. TRAF adaptor proteins have been shown to bind to this receptor and transduce the signals leading to activation of NF-kappaB. [provided by RefSeq, Jul 2008]

TNFRSF9 Gene-Disease associations (from GenCC):

• immunodeficiency 109 with lymphoproliferation

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-7938903-T-G is Benign according to our data. Variant chr1-7938903-T-G is described in ClinVar as Benign. ClinVar VariationId is 2688134.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001561.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF9	NM_001561.6	MANE Select	c.101-75A>C		intron	N/A	NP_001552.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF9	ENST00000377507.8	TSL:1 MANE Select	c.101-75A>C		intron	N/A	ENSP00000366729.3
	TNFRSF9	ENST00000875592.1		c.101-75A>C		intron	N/A	ENSP00000545651.1
	TNFRSF9	ENST00000674210.1		c.101-75A>C		intron	N/A	ENSP00000501326.1

Frequencies

GnomAD3 genomes AF: 0.972 AC: 148033 AN: 152228 Hom.: 72024 Cov.: 33

Gnomad AFR AF: 0.994

Gnomad AMI AF: 0.995

Gnomad AMR AF: 0.985

Gnomad ASJ AF: 0.969

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.991

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.958

Gnomad OTH AF: 0.977

GnomAD4 exome AF: 0.965 AC: 830397 AN: 860874 Hom.: 400647 AF XY: 0.965 AC XY: 425073 AN XY: 440396

African (AFR) AF: 0.994 AC: 20867 AN: 20992

American (AMR) AF: 0.990 AC: 31458 AN: 31770

Ashkenazi Jewish (ASJ) AF: 0.972 AC: 18513 AN: 19046

East Asian (EAS) AF: 1.00 AC: 35232 AN: 35240

South Asian (SAS) AF: 0.988 AC: 57495 AN: 58172

European-Finnish (FIN) AF: 0.940 AC: 44398 AN: 47220

Middle Eastern (MID) AF: 0.992 AC: 4346 AN: 4382

European-Non Finnish (NFE) AF: 0.959 AC: 580355 AN: 605024

Other (OTH) AF: 0.967 AC: 37733 AN: 39028

GnomAD4 genome AF: 0.972 AC: 148152 AN: 152346 Hom.: 72084 Cov.: 33 AF XY: 0.973 AC XY: 72469 AN XY: 74496

African (AFR) AF: 0.994 AC: 41308 AN: 41572

American (AMR) AF: 0.985 AC: 15076 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.969 AC: 3366 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5192 AN: 5194

South Asian (SAS) AF: 0.991 AC: 4786 AN: 4828

European-Finnish (FIN) AF: 0.942 AC: 10008 AN: 10622

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 0.958 AC: 65149 AN: 68036

Other (OTH) AF: 0.977 AC: 2067 AN: 2116

Alfa AF: 0.963 Hom.: 49466

Bravo AF: 0.977

Asia WGS AF: 0.996 AC: 3464 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.5
DANN	Benign	0.22
PhyloP100		0.29
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: rs226476; hg19: chr1-7998963;