chr8-130780534-A-G

Variant names:

• chr8-130780534-A-G
• rs147371587
• NM_001115.3:c.3612T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001115.3(ADCY8):​c.3612T>C​(p.Asn1204Asn) variant causes a synonymous change. The variant allele was found at a frequency of 0.00138 in 1,613,978 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0073 (14 hom., cov: 32)
  • Exomes 𝑓: 0.00076 (13 hom.)
• Consequence: ADCY8 NM_001115.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.82

Genes affected

ADCY8 (HGNC:239): (adenylate cyclase 8) Adenylate cyclase is a membrane bound enzyme that catalyses the formation of cyclic AMP from ATP. The enzymatic activity is under the control of several hormones, and different polypeptides participate in the transduction of the signal from the receptor to the catalytic moiety. Stimulatory or inhibitory receptors (Rs and Ri) interact with G proteins (Gs and Gi) that exhibit GTPase activity and they modulate the activity of the catalytic subunit of the adenylyl cyclase [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 8-130780534-A-G is Benign according to our data. Variant chr8-130780534-A-G is described in ClinVar as [Benign]. Clinvar id is 713271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00734 (1117/152106) while in subpopulation AFR AF = 0.0255 (1058/41486). AF 95% confidence interval is 0.0242. There are 14 homozygotes in GnomAd4. There are 525 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
• BS2: High AC in GnomAd4 at 1117 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY8	NM_001115.3	c.3612T>C	p.Asn1204Asn	synonymous_variant	Exon 18 of 18	ENST00000286355.10	NP_001106.1
ADCY8	XM_005250769.4	c.3522T>C	p.Asn1174Asn	synonymous_variant	Exon 17 of 17		XP_005250826.1
ADCY8	XM_006716501.4	c.3414T>C	p.Asn1138Asn	synonymous_variant	Exon 17 of 17		XP_006716564.1
ADCY8	XM_017013006.2	c.3324T>C	p.Asn1108Asn	synonymous_variant	Exon 16 of 16		XP_016868495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY8	ENST00000286355.10	c.3612T>C	p.Asn1204Asn	synonymous_variant	Exon 18 of 18	1	NM_001115.3	ENSP00000286355.5
ADCY8	ENST00000377928.7	c.3219T>C	p.Asn1073Asn	synonymous_variant	Exon 15 of 15	1		ENSP00000367161.3

Frequencies

GnomAD3 genomes AF: 0.00734 AC: 1116 AN: 151988 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0255

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.000866

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00189 AC: 476 AN: 251210 AF XY: 0.00146

Gnomad AFR exome AF: 0.0257

Gnomad AMR exome AF: 0.000838

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.000759 AC: 1110 AN: 1461872 Hom.: 13 Cov.: 35 AF XY: 0.000671 AC XY: 488 AN XY: 727236

Gnomad4 AFR exome AF: 0.0264 AC: 884 AN: 33480

Gnomad4 AMR exome AF: 0.000961 AC: 43 AN: 44724

Gnomad4 ASJ exome AF: 0.0000765 AC: 2 AN: 26136

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39694

Gnomad4 SAS exome AF: 0.000151 AC: 13 AN: 86258

Gnomad4 FIN exome AF: 0.0000374 AC: 2 AN: 53420

Gnomad4 NFE exome AF: 0.0000495 AC: 55 AN: 1111996

Gnomad4 Remaining exome AF: 0.00174 AC: 105 AN: 60396

GnomAD4 genome AF: 0.00734 AC: 1117 AN: 152106 Hom.: 14 Cov.: 32 AF XY: 0.00706 AC XY: 525 AN XY: 74346

Gnomad4 AFR AF: 0.0255 AC: 0.0255026 AN: 0.0255026

Gnomad4 AMR AF: 0.00216 AC: 0.00215912 AN: 0.00215912

Gnomad4 ASJ AF: 0.000866 AC: 0.000865551 AN: 0.000865551

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.0000735 AC: 0.0000735337 AN: 0.0000735337

Gnomad4 OTH AF: 0.00615 AC: 0.00614948 AN: 0.00614948

Alfa AF: 0.00436 Hom.: 3

Bravo AF: 0.00833

Asia WGS AF: 0.000578 AC: 2 AN: 3476

EpiCase AF: 0.000109

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 23, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.9
DANN	Benign	0.62
Mutation Taster		=100/0	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

Publications

LitVar

Other links and lift over

dbSNP: rs147371587; hg19: chr8-131792780;