rs114907619

chr19-44703354-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001039213.4(CEACAM16):c.43T>C(p.Phe15Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00051 in 1,608,808 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0027 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00028 (1 hom.)
• Consequence: CEACAM16 NM_001039213.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.385

Genes affected

CEACAM16 (HGNC:31948): (CEA cell adhesion molecule 16, tectorial membrane component) The protein encoded by this gene is a secreted glycoprotein that in mouse interacts with tectorial membrane proteins in the inner ear. The encoded adhesion protein is found in cochlear outer hair cells and appears to be important for proper hearing over an extended frequency range. Defects in this gene likely are a cause of non-syndromic autosomal dominant hearing loss. [provided by RefSeq, May 2012]

CEACAM16-AS1 (HGNC:55317): (CEACAM16, CEACAM19 and PVR antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004791856).
• BP6: Variant 19-44703354-T-C is Benign according to our data. Variant chr19-44703354-T-C is described in ClinVar as [Benign]. Clinvar id is 226507.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 = 0.00272 (414/152270) while in subpopulation AFR AF= 0.00909 (378/41562). AF 95% confidence interval is 0.00834. There are 2 homozygotes in gnomad4. There are 201 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEACAM16	NM_001039213.4	c.43T>C	p.Phe15Leu	missense_variant	3/7	ENST00000587331.7
CEACAM16	XM_017026795.2	c.43T>C	p.Phe15Leu	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEACAM16	ENST00000587331.7	c.43T>C	p.Phe15Leu	missense_variant	3/7	1	NM_001039213.4	P1
CEACAM16-AS1	ENST00000662585.1	n.382-4177A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00272 AC: 414 AN: 152152 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00912

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000769 AC: 189 AN: 245798 Hom.: 1 AF XY: 0.000599 AC XY: 80 AN XY: 133594

Gnomad AFR exome AF: 0.0104

Gnomad AMR exome AF: 0.000814

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: 0.000501

GnomAD4 exome AF: 0.000279 AC: 407 AN: 1456538 Hom.: 1 Cov.: 32 AF XY: 0.000236 AC XY: 171 AN XY: 723544

Gnomad4 AFR exome AF: 0.00964

Gnomad4 AMR exome AF: 0.000963

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.000566

GnomAD4 genome AF: 0.00272 AC: 414 AN: 152270 Hom.: 2 Cov.: 32 AF XY: 0.00270 AC XY: 201 AN XY: 74468

Gnomad4 AFR AF: 0.00909

Gnomad4 AMR AF: 0.00222

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000468 Hom.: 1

Bravo AF: 0.00318

ESP6500AA AF: 0.00823 AC: 33

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000918 AC: 111

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 30, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 20, 2023	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Nov 24, 2014

Phe15Leu in exon 3 of CEACAM16: This variant is not expected to have clinical si gnificance because it has been identified in 0.8% (33/4008) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs114907619). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.79
Cadd	Benign	4.8
Dann	Benign	0.19
DEOGEN2	Benign	0.014	T;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.026	N
MetaRNN	Benign	0.0048	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.17	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.38	T
Sift4G	Benign	0.74	T;T
Vest4		0.14
MVP		0.030
MPC		0.15
ClinPred		0.016	T
GERP RS		-9.4
Varity_R		0.019
gMVP		0.19

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: rs114907619; hg19: chr19-45206624;