Genetic Variant NM_001114.5:c.2448+81T>G (chr16-50311867-T-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001114.5(ADCY7):c.2448+81T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 20)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

ADCY7
NM_001114.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.255

Publications

6 publications found

Variant links:

Genes affected

ADCY7 (HGNC:238): (adenylate cyclase 7) This gene encodes a membrane-bound adenylate cyclase that catalyses the formation of cyclic AMP from ATP and is inhibitable by calcium. The product of this gene is a member of the adenylyl cyclase class-4/guanylyl cyclase enzyme family that is characterized by the presence of twelve membrane-spanning domains in its sequences. Several transcript variants have been observed for this gene, but the full-length natures of only two have been determined so far. [provided by RefSeq, Oct 2013]

ADCY7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY7	NM_001114.5 link	c.2448+81T>G		intron_variant	Intron 20 of 25	ENST00000673801.1	NP_001105.1	P51828Q86YI0

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADCY7	ENST00000673801.1 link	c.2448+81T>G	intron_variant	Intron 20 of 25		NM_001114.5	ENSP00000501053.1	P51828
ADCY7	ENST00000254235.7 link	c.2448+81T>G	intron_variant	Intron 19 of 24	1		ENSP00000254235.3	P51828
ADCY7	ENST00000394697.7 link	c.2448+81T>G	intron_variant	Intron 20 of 25	5		ENSP00000378187.2	P51828
ADCY7	ENST00000673973.1 link	n.*820+81T>G	intron_variant	Intron 20 of 25			ENSP00000501223.1	H3BQ93

Frequencies

GnomAD3 genomes

AF:

0.0000528

AC:

AN:

132576

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000285

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000740

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000290

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000475

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000339

AC:

AN:

1150830

Hom.:

Cov.:

AF XY:

0.0000360

AC XY:

AN XY:

582956

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

26850

American (AMR)

AF:

0.0000232

AC:

AN:

43108

Ashkenazi Jewish (ASJ)

AF:

0.000174

AC:

AN:

23006

East Asian (EAS)

AF:

0.00

AC:

AN:

29696

South Asian (SAS)

AF:

0.0000258

AC:

AN:

77540

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45560

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4026

European-Non Finnish (NFE)

AF:

0.0000317

AC:

AN:

852280

Other (OTH)

AF:

0.000103

AC:

AN:

48764

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.316

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000527

AC:

AN:

132726

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

63732

show subpopulations

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

African (AFR)

AF:

0.0000284

AC:

AN:

35198

American (AMR)

AF:

0.0000739

AC:

AN:

13530

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3304

East Asian (EAS)

AF:

0.00

AC:

AN:

3568

South Asian (SAS)

AF:

0.00

AC:

AN:

4174

European-Finnish (FIN)

AF:

0.000290

AC:

AN:

6900

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.0000475

AC:

AN:

63094

Other (OTH)

AF:

0.00

AC:

AN:

1858

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000774357), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

35501

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.049

(source)

DANN

Benign

0.55

PhyloP100

-0.26

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over