rs374901597

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_139320.2(CHRFAM7A):c.703G>A(p.Gly235Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000106 in 151,478 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000018 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CHRFAM7A
NM_139320.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.60

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRFAM7A	NM_139320.2 link	c.703G>A	p.Gly235Ser	missense_variant	Exon 9 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.703G>A	p.Gly235Ser	missense_variant	Exon 9 of 10	1	NM_139320.2	ENSP00000299847.3	Q494W8
CHRFAM7A	ENST00000401522.7 link	c.430G>A	p.Gly144Ser	missense_variant	Exon 10 of 11	1		ENSP00000385389.3	A0A0A6YYA8
CHRFAM7A	ENST00000397827.7 link	c.430G>A	p.Gly144Ser	missense_variant	Exon 8 of 9	5		ENSP00000380927.3	A0A0A6YYA8
CHRFAM7A	ENST00000692430.1 link	n.655G>A		non_coding_transcript_exon_variant	Exon 4 of 5

Frequencies

GnomAD3 genomes

AF:

0.000106

AC:

AN:

151360

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000389

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000361

AC:

AN:

249398

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

134878

show subpopulations

Gnomad AFR exome

AF:

0.000562

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000179

AC:

AN:

1456418

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

724642

show subpopulations

Gnomad4 AFR exome

AF:

0.000661

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.03e-7

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.000106

AC:

AN:

151478

Hom.:

Cov.:

AF XY:

0.0000810

AC XY:

AN XY:

74068

show subpopulations

Gnomad4 AFR

AF:

0.000388

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ESP6500AA

AF:

0.000685

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000908

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.703G>A (p.G235S) alteration is located in exon 9 (coding exon 7) of the CHRFAM7A gene. This alteration results from a G to A substitution at nucleotide position 703, causing the glycine (G) at amino acid position 235 to be replaced by a serine (S). 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

Benign

0.087

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;.;.

Eigen

Benign

0.15

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.95

D;D;.

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.64

D;D;D

MetaSVM

Uncertain

0.11

MutationAssessor

Uncertain

2.1

M;.;.

PROVEAN

Benign

-1.7

N;N;N

REVEL

Uncertain

0.49

Sift

Benign

0.21

T;T;T

Sift4G

Benign

0.36

T;T;T

Polyphen

0.63

P;.;.

Vest4

0.73

MVP

0.60

ClinPred

0.089

GERP RS

3.2

Varity_R

0.20

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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