rs200611153

Variant names:

• chr15-30372286-A-G
• rs200611153
• NM_139320.2:c.384T>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_139320.2(CHRFAM7A):​c.384T>C​(p.Pro128Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000038 (0 hom., cov: 14)
  • Exomes 𝑓: 0.0000094 (5 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHRFAM7A NM_139320.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.710
• 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 15-30372286-A-G is Benign according to our data. Variant chr15-30372286-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 730496.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.71 with no splicing effect.

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.384T>C	p.Pro128Pro	synonymous	Exon 7 of 10	NP_647536.1	Q494W8
	CHRFAM7A	NM_148911.1		c.111T>C	p.Pro37Pro	synonymous	Exon 6 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.384T>C	p.Pro128Pro	synonymous	Exon 7 of 10	ENSP00000299847.3	Q494W8
	CHRFAM7A	ENST00000401522.7	TSL:1	c.111T>C	p.Pro37Pro	synonymous	Exon 8 of 11	ENSP00000385389.3	A0A0A6YYA8
	CHRFAM7A	ENST00000853243.1		c.384T>C	p.Pro128Pro	synonymous	Exon 8 of 11	ENSP00000523302.1

Frequencies

GnomAD3 genomes AF: 0.0000378 AC: 4 AN: 105918 Hom.: 0 Cov.: 14

Gnomad AFR AF: 0.0000414

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: 0.0000593

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000975 AC: 2 AN: 205178 AF XY: 0.0000180

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000941 AC: 11 AN: 1168882 Hom.: 5 Cov.: 34 AF XY: 0.0000137 AC XY: 8 AN XY: 582388

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 22690

American (AMR) AF: 0.0000521 AC: 2 AN: 38388

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19316

East Asian (EAS) AF: 0.00 AC: 0 AN: 38454

South Asian (SAS) AF: 0.00 AC: 0 AN: 74092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42702

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4524

European-Non Finnish (NFE) AF: 0.0000102 AC: 9 AN: 880486

Other (OTH) AF: 0.00 AC: 0 AN: 48230

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000377 AC: 4 AN: 105990 Hom.: 0 Cov.: 14 AF XY: 0.00 AC XY: 0 AN XY: 51566

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000413 AC: 1 AN: 24204

American (AMR) AF: 0.00 AC: 0 AN: 10758

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2432

East Asian (EAS) AF: 0.00 AC: 0 AN: 4734

South Asian (SAS) AF: 0.00 AC: 0 AN: 3592

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 208

European-Non Finnish (NFE) AF: 0.0000593 AC: 3 AN: 50570

Other (OTH) AF: 0.00 AC: 0 AN: 1470

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0198 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.67
DANN	Benign	0.38
PhyloP100		-0.71
Mutation Taster		=99/1	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: rs200611153; hg19: chr15-30664489; COSMIC: COSV55396841; COSMIC: COSV55396841;