rs2058751485

Variant names:

• chr15-30362661-T-C
• rs2058751485
• NM_139320.2:c.871A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-30362661-T-C
• chr15-30362661-T-G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_139320.2(CHRFAM7A):​c.871A>G​(p.Asn291Asp) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 1)
• Consequence: CHRFAM7A NM_139320.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.33
• Publications: 0 publications found

Genes affected

CHRFAM7A (HGNC:15781): (CHRNA7 (exons 5-10) and FAM7A (exons A-E) fusion) The nicotinic acetylcholine receptors (nAChRs) are members of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. The family member CHRNA7, which is located on chromosome 15 in a region associated with several neuropsychiatric disorders, is partially duplicated and forms a hybrid with a novel gene from the family with sequence similarity 7 (FAM7A). Alternative splicing has been observed, and two variants exist, for this hybrid gene. The N-terminally truncated products predicted by the largest open reading frames for each variant would lack the majority of the neurotransmitter-gated ion-channel ligand binding domain but retain the transmembrane region that forms the ion channel. Although current evidence supports transcription of this hybrid gene, translation of the nicotinic acetylcholine receptor-like protein-encoding open reading frames has not been confirmed. [provided by RefSeq, Jul 2008]

LINC02249 (HGNC:32351): (long intergenic non-protein coding RNA 2249)

LOC105370751 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.31683424).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139320.2. 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
	CHRFAM7A	NM_139320.2	MANE Select	c.871A>G	p.Asn291Asp	missense	Exon 10 of 10	NP_647536.1	Q494W8
	CHRFAM7A	NM_148911.1		c.598A>G	p.Asn200Asp	missense	Exon 9 of 9	NP_683709.1	P36544

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRFAM7A	ENST00000299847.7	TSL:1 MANE Select	c.871A>G	p.Asn291Asp	missense	Exon 10 of 10	ENSP00000299847.3	Q494W8
	CHRFAM7A	ENST00000401522.7	TSL:1	c.598A>G	p.Asn200Asp	missense	Exon 11 of 11	ENSP00000385389.3	A0A0A6YYA8
	CHRFAM7A	ENST00000853243.1		c.871A>G	p.Asn291Asp	missense	Exon 11 of 11	ENSP00000523302.1

Frequencies

GnomAD3 genomes Cov.: 1

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.083
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.32	T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Benign	1.8	L
PhyloP100		7.3
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.41
Sift	Benign	0.66	T
Sift4G	Benign	0.35	T
Polyphen		1.0	D
Vest4		0.47
MutPred		0.39		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.57
ClinPred		0.98	D
GERP RS		3.1
Varity_R		0.13
gMVP		0.42
Mutation Taster		=84/16	polymorphism

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: rs2058751485; hg19: chr15-30654864;