rs770597479

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_139320.2(CHRFAM7A):c.473C>T(p.Ala158Val) 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: 𝑓 0.00034 ( 2 hom., cov: 10)

Exomes 𝑓: 0.00053 ( 166 hom. )

Failed GnomAD Quality Control

Consequence

CHRFAM7A
NM_139320.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.21

Variant links:

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]

CHRFAM7A links:

LOC105370751 (HGNC:):

LOC105370751 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3928598).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRFAM7A	NM_139320.2 link	c.473C>T	p.Ala158Val	missense_variant	Exon 7 of 10	ENST00000299847.7	NP_647536.1	Q494W8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHRFAM7A	ENST00000299847.7 link	c.473C>T	p.Ala158Val	missense_variant	Exon 7 of 10	1	NM_139320.2	ENSP00000299847.3	Q494W8
CHRFAM7A	ENST00000401522.7 link	c.200C>T	p.Ala67Val	missense_variant	Exon 8 of 11	1		ENSP00000385389.3	A0A0A6YYA8
CHRFAM7A	ENST00000397827.7 link	c.200C>T	p.Ala67Val	missense_variant	Exon 6 of 9	5		ENSP00000380927.3	A0A0A6YYA8
CHRFAM7A	ENST00000692430.1 link	n.425C>T		non_coding_transcript_exon_variant	Exon 2 of 5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

79544

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000784

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000370

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000471

Gnomad OTH

AF:

0.000965

GnomAD3 exomes

AF:

0.000382

AC:

AN:

162416

Hom.:

AF XY:

0.000470

AC XY:

AN XY:

87284

show subpopulations

Gnomad AFR exome

AF:

0.000225

Gnomad AMR exome

AF:

0.000379

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00118

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000371

Gnomad OTH exome

AF:

0.000506

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000526

AC:

574

AN:

1090930

Hom.:

166

Cov.:

AF XY:

0.000574

AC XY:

314

AN XY:

547080

show subpopulations

Gnomad4 AFR exome

AF:

0.000141

Gnomad4 AMR exome

AF:

0.000427

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00117

Gnomad4 FIN exome

AF:

0.0000705

Gnomad4 NFE exome

AF:

0.000564

Gnomad4 OTH exome

AF:

0.000240

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000339

AC:

AN:

79574

Hom.:

Cov.:

AF XY:

0.000346

AC XY:

AN XY:

37618

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000783

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000371

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000471

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000337

Hom.:

ExAC

AF:

0.000332

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.473C>T (p.A158V) alteration is located in exon 7 (coding exon 5) of the CHRFAM7A gene. This alteration results from a C to T substitution at nucleotide position 473, causing the alanine (A) at amino acid position 158 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Benign

-0.052

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.39

T;.;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.96

D;D;.

M_CAP

Benign

0.035

MetaRNN

Benign

0.39

T;T;T

MetaSVM

Uncertain

0.48

MutationAssessor

Uncertain

2.9

M;.;.

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Pathogenic

0.70

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.059

T;D;D

Polyphen

1.0

D;.;.

Vest4

0.77

MVP

0.54

ClinPred

0.21

GERP RS

2.6

Varity_R

0.51

gMVP

0.78

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over