7-137882595-T-A

Variant names:

• chr7-137882595-T-A
• rs199561057
• NM_194071.4:c.1304A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_194071.4(CREB3L2):​c.1304A>T​(p.His435Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H435R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CREB3L2 NM_194071.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 0 publications found

Genes affected

CREB3L2 (HGNC:23720): (cAMP responsive element binding protein 3 like 2) This gene encodes a member of the oasis bZIP transcription factor family. Members of this family can dimerize but form homodimers only. The encoded protein is a transcriptional activator. Translocations between this gene on chromosome 7 and the gene fused in sarcoma on chromosome 16 can be found in some tumors. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20927262).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194071.4. 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
	CREB3L2	NM_194071.4	MANE Select	c.1304A>T	p.His435Leu	missense	Exon 11 of 12	NP_919047.2	Q70SY1-1
	CREB3L2	NM_001318246.2		c.1115A>T	p.His372Leu	missense	Exon 11 of 12	NP_001305175.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CREB3L2	ENST00000330387.11	TSL:1 MANE Select	c.1304A>T	p.His435Leu	missense	Exon 11 of 12	ENSP00000329140.6	Q70SY1-1
	CREB3L2	ENST00000898368.1		c.1298A>T	p.His433Leu	missense	Exon 11 of 12	ENSP00000568427.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1457698 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724450

African (AFR) AF: 0.00 AC: 0 AN: 33392

American (AMR) AF: 0.00 AC: 0 AN: 44480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25952

East Asian (EAS) AF: 0.00 AC: 0 AN: 39588

South Asian (SAS) AF: 0.00 AC: 0 AN: 86008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1108998

Other (OTH) AF: 0.00 AC: 0 AN: 60172

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.0
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.058
Sift	Benign	0.25	T
Sift4G	Benign	0.30	T
Polyphen		0.70	P
Vest4		0.38
MutPred		0.22		Gain of catalytic residue at H435 (P = 0.0654)
MVP		0.43
MPC		0.12
ClinPred		0.38	T
GERP RS		1.2
Varity_R		0.16
gMVP		0.36
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs199561057; hg19: chr7-137567341;